Search Subject Areas | Preprints.org

Preprint ARTICLE | doi:10.20944/preprints202003.0226.v1

Potential Inhibitor of COVID-19 Main Protease (M^pro) From Several Medicinal Plant Compounds by Molecular Docking Study

Siti Khaerunnisa, Hendra Kurniawan, Rizki Awaluddin, Suhartati Suhartati, Soetjipto Soetjipto

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-2019; Mpro; 6LU7; medicinal plant compounds; docking

Online: 13 March 2020 (03:19:02 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202004.0457.v1

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Anton S.M. Dofferhoff, Ianthe Piscaer, Leon J. Schurgers, Jona Walk, Jody M.W. van den Ouweland, Tilman M. Hackeng, Petra Lux, Cecile Maassen, Esther G.A. Karssemeijer, Emiel F.M. Wouters, Rob Janssen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; vitamin K; vitamin K antagonists; SARS-CoV-2; matrix Gla protein; desmosine; protein C; protein S

Online: 25 April 2020 (03:13:45 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202003.0214.v1

Revealing the Potency of Citrus and Galangal Constituents to Halt SARS-CoV-2 Infection

Rohmad Yudi Utomo, Muthi' Ikawati, Edy Meiyanto

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-Cov-2; Citrus sp.; Galangal; Curcuma sp.; Sappan wood

Online: 12 March 2020 (13:59:40 CET)

Show abstract| Download PDF| Share

Preprint HYPOTHESIS | doi:10.20944/preprints202003.0279.v1

Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now

Raymond Chang, Wei-Zen Sun

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: chloroquine; COVID-19; SARS-CoV2; antiviral; viral prophylaxis

Online: 17 March 2020 (15:57:38 CET)

Show abstract| Download PDF| Share

Preprint BRIEF REPORT | doi:10.20944/preprints202002.0242.v2

Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking

Yu-Chuan Chang, Yi-An Tung, Ko-Han Lee, Ting-Fu Chen, Yu-Chun Hsiao, Hung-Ching Chang, Tsung-Ting Hsieh, Chan-Hung Su, Su-Shia Wang, Jheng-Ying Yu, Shang-shung Shih, Yu-Hsiang Lin, Yin-Hung Lin, Yi-Chin Ethan Tu, Chun-Hua Hsu, Hsueh-Fen Juan, Chun-Wei Tung, Chien-Yu Chen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; molecular docking; HIV protease inhibitor; nucleotide analogues

Online: 29 February 2020 (12:43:40 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202004.0457.v2

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Anton S.M. Dofferhoff, Ianthe Piscaer, Leon J. Schurgers, Jona Walk, Jody M.W. van den Ouweland, Tilman M. Hackeng, Pim A. de Jong, Reinoud Gosens, Petra Lux, Henny van Daal, Cecile Maassen, Esther G.A. Maassen, Loes E.M. Kistemaker, Cees Vermeer, Emiel F.M. Wouters, Rob Janssen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Covid-19; desmosine; dp-ucMGP; elastic fibers; factor II; matrix Gla protein; PIVKA-II; protein S; vitamin K; vitamin K antagonist

Online: 29 May 2020 (04:16:20 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint HYPOTHESIS | doi:10.20944/preprints202004.0090.v1

Hydroxychloroquine as an Aerosol Might Markedly Reduce and Even Prevent Severe Clinical Symptoms after SARS-CoV-2 Infection

Ansgar Klimke, Gudrun Hefner, Bianca Will, Ursula Voss

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19: hydroxychloroquine aerosol; pharmacotherapy; prevention; SARS-CoV-2

Online: 7 April 2020 (11:11:09 CEST)

Show abstract| Download PDF| Share

Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.

Preprint BRIEF REPORT | doi:10.20944/preprints202002.0242.v1

Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking

Yu-Chuan Chang, Yi-An Tung, Ko-Han Lee, Ting-Fu Chen, Yu-Chun Hsiao, Hung-Ching Chang, Tsung-Ting Hsieh, Chan-Hung Su, Su-Shia Wang, Jheng-Ying Yu, Shang-shung Shih, Yu-Hsiang Lin, Yin-Hung Lin, Yi-Chin Ethan Tu, Chun-Wei Tung, Chien-Yu Chen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; molecular docking; HIV protease inhibitor; nucleotide analogues

Online: 17 February 2020 (07:28:31 CET)

Show abstract| Download PDF| Share

Preprint CONCEPT PAPER | doi:10.20944/preprints202004.0432.v1

Nitazoxanide/Azithromycin Combination for COVID-19: A Suggested New Protocol for COVID-19 Early Management

Mina Kelleni

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS CoV-2; COVID-19; Nitazoxanide; Azithromycin; Interferons

Online: 24 April 2020 (09:24:23 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202003.0302.v1

Focusing on the Unfolded Protein Response and Autophagy Related Pathways to Reposition Common Approved Drugs against COVID-19

Serguei Nabirotchkin, Alex E. Peluffo, Jan Bouaziz, Daniel Cohen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-2019; SARS-CoV-2; 2019-nCoV; repositioning; UPR/Autophagy; real-world evidence; pathways

Online: 20 March 2020 (03:55:55 CET)

Show abstract| Download PDF| Supplementary Files| Share

More than 179,000 individuals have fallen ill of the Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus, which first emerged in China less than four months ago in December 2019. As of today, there exist no approved treatments against COVID-19. Vaccines are being developed, but they will take time, at least one year, to reach the population. Drug repositioning represents a fast track because already approved medicines have been broadly tested through multiple trials. We developed a repositioning strategy that mostly leads to candidates that are commonly used. The advantages are that they will facilitate proof of concept in humans through a “real-world evidence” approach and should be rapidly available to the population. We focus on the established research results that the unfolded protein response (UPR) and autophagy pathways of the host cells are essential to the life cycle of previously known coronaviruses. We performed the relevant bioinformatics analysis to understand and confirm if SARS-CoV-2 may interact with these druggable pathways. Based on these considerations, we prioritized two additional druggable pathways, which are important to the viral life cycle and tightly connected to UPR/autophagy signaling: the mitochondrial permeability transition pores (MPTP) and NLRP-3 inflammasome pathways. These four important pathways are perturbed in most major common diseases and have therefore been targeted by numerous broadly prescribed drugs. We have identified 97 approved drugs that are known to modulate these four identified pathways, and which represent, therefore, interesting repositioning candidates. Although it is indisputable that these drugs should never be used for immediate self-medication against COVID-19, we notice that some of them could also be prescribed to individuals who have COVID-19 comorbidities (e.g., hypertension). It is debated if these comorbidities are linked to the pathology itself (e.g., hypertension) or the drugs used to treat the pathology (e.g., sartans). Therefore, relevant preclinical tests and massive electronic health records (i.e., real-world evidence) must be used to pre-screen them and check the COVID-19 prognosis of individuals taking these drugs.

Preprint HYPOTHESIS | doi:10.20944/preprints202004.0013.v1

High Risk COVID-19: Potential Intervention at Multiple Points in the COVID-19 Disease Process Via Prophylactic Treatment with Azithromycin or Bee Derived Products

Janice Block

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; azithromycin; bee

Online: 2 April 2020 (11:06:47 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202005.0178.v1

SARS-CoV-2 and the Possible Connection to ERs, ACE2 and RAGE: Focus on Susceptibility Factors

Roberta Sessa Stilhano, Angelica Jardim Costa, Michelle Sayuri Nishino, Shahin Shams, Cynthia Silva Bartolomeo, Ana Cristina Breithaupt-Faloppa, Eduardo Alexandre Silva, Ana Lopez Ramirez, Carla Maximo Prado, Rodrigo Portes Ureshino

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; estrogen; RAGE; ACE2

Online: 10 May 2020 (17:46:13 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202002.0047.v1

Possible Inhibitors of ACE2, the Receptor of 2019-nCoV

Qinghua Cui, Chuanbo Huang, Xiangwen Ji, Wanlu Zhang, Fenghong Zhang, Liang Wang

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2019-nCoV; therapeutic strategies; drug; ACE2

Online: 4 February 2020 (10:59:25 CET)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202004.0007.v1

A Coadunation of Biological and Mathematical Perspectives on the Pandemic COVID-19: A Review

Sahar Qazi, Kayenat Sheikh, Mo Faheem, Arshad Khan, Khalid Raza

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: nCov-19, COVID-19, coronavirus, SARS-CoV

Online: 1 April 2020 (09:30:00 CEST)

Show abstract| Download PDF| Share

Preprint BRIEF REPORT | doi:10.20944/preprints201707.0079.v1

A Simple Way to Reduce the Risk of Cancer of the Oral Cavity, Pharynx, Larynx and Esophagus in Alcohol Users

Emilio Guillén-Mancina, José Manuel Calderón-Montaño, Miguel López-Lázaro

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: alcohol consumption; tobacco smoking; carcinogenesis; addiction; stem cells; stem cell division theory of cancer

Online: 27 July 2017 (12:34:00 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202204.0296.v1

Efficacy of Short-Term High Dose Pulsed Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases and Literature Review

Richard I. Horowitz, Phyllis R. Freeman

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: dapsone; disulfiram; chronic Lyme disease; Post-Treatment Lyme Disease Syndrome; babesia; bartonella; persisters; biofilms.

Online: 29 April 2022 (10:12:41 CEST)

Show abstract| Download PDF| Share

Preprint COMMUNICATION | doi:10.20944/preprints202002.0418.v2

Virtual Screening Based Prediction of Potential Drugs for COVID-19

Sekhar Talluri

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: virtual screening; molecular docking; drug repurposing; drug repositioning; anti-viral drugs; Coronavirus; COVID-19; 2019-nCoV; SARS-CoV-2

Online: 9 March 2020 (02:29:04 CET)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints202003.0413.v1

Ontological and Bioinformatic Analysis of Anti-Coronavirus Drugs and Their Implication for Drug Repurposing against COVID-19

Yingtong Liu, Wallace K.B. Chan, Zhigang Wang, Junguk Hur, Jiangan Xie, Hong Yu, Yongqun He

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: coronavirus; drug; COVID-19; SARS; MERS; ontology; ChEBI; NDF-RT; DrON; bioinformatics

Online: 29 March 2020 (01:58:40 CET)

Show abstract| Download PDF| Share

Coronavirus-infected diseases have posed great threats to human health. In past years, highly infectious coronavirus-induced diseases, including COVID-19, SARS, and MERS, have resulted in world-wide severe infections. Our literature annotations identified 110 chemical drugs and 26 antibodies effective against at least one human coronavirus infection in vitro or in vivo. Many of these drugs inhibit viral entry to cells and viral replication inside cells or modulate host immune responses. Many antimicrobial drugs, including antimalarial (e.g., chloroquine and mefloquine) and antifungal (e.g., terconazole and rapamycin) drugs as well as antibiotics (e.g., teicoplanin and azithromycin) were associated with anti-coronavirus activity. A few drugs, including remdesivir, chloroquine, favipiravir, and tocilizumab, have already been reported to be effective against SARS-CoV-2 infection in vitro or in vivo. After mapping our identified drugs to three ontologies ChEBI, NDF-RT, and DrON, many features such as roles and mechanisms of action (MoAs) of these drugs were identified and categorized. For example, out of 57 drugs with MoA annotations in NDF-RT, 47 have MoAs of different types of inhibitors and antagonists. A total of 29 anticoronaviral drugs are anticancer drugs with the antineoplastic role. Two clustering analyses, one based on ChEBI-based semantic similarity, the other based on drug chemical similarity, were performed to cluster 110 drugs to new categories. Moreover, differences in physicochemical properties among the drugs were found between those inhibiting viral entry and viral replication. A total of 163 host genes were identified as the known targets of 68 anti-coronavirus drugs, resulting in a network of 428 interactions among these drugs and targets. Chlorpromazine, dasatinib, and anisomycin are the hubs of the drug-target network with the highest number of connected target proteins. Many enriched pathways such as calcium signaling and neuroactive ligand-receptor interaction pathways were identified. These findings may be used to facilitate drug repurposing against COVID-19.

Preprint ARTICLE | doi:10.20944/preprints202202.0132.v1

Differential Acellular Reactive Oxygen Species (ROS) Generation by E-cigarettes Containing Tobacco-Free Nicotine (TFN) and Tobacco-Derived Nicotine

Shaiesh Yogeswaran, Irfan Rahman

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Tobacco Free Nicotine (TFN); Synthetic Nicotine; Tobacco-derived Nicotine; vape-bar; Electronic Nicotine Delivery Systems; Reactive Oxygen Species (ROS)

Online: 9 February 2022 (10:37:28 CET)

Show abstract| Download PDF| Share

Working Paper HYPOTHESIS

Paracetamol use in COVID-19: friend or enemy?

Piero Sestili, Carmela Fimognari

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; paracetamol; NSAIDs; inflammation; lung injury; oxidative damage; glutathione; antioxidant.

Online: 7 August 2020 (11:02:20 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201910.0178.v1

Essential Oils with High Activity Against Stationary Phase Bartonella Henselae

Xiao Ma, Wanliang Shi, Ying Zhang

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: essential oils; Bartonella henselae; persisters; stationary phase; antimicrobial activity

Online: 16 October 2019 (05:18:55 CEST)

Show abstract| Download PDF| Share

Bartonella henselae is a fastidious Gram-negative intracellular bacterium which can cause cat scratch disease, endocarditis in humans and animals as well as other complications, leading to acute or chronic infections. The current treatment for Bartonella infections is not very effective due to antibiotic resistance and also persistence. To develop better therapies for persistent and chronic Bartonella infections, in this study, with the help of SYBR Green I/PI viability assay, we performed a high-throughput screening of an essential oil library against stationary phase B. henselae. We successfully identified 32 essential oils that had high activity, including four essential oils extracted from Citrus plants, three from Origanum, three from Cinnamomum, two from Pelargonium and two from Melaleuca, as well as frankincense, ylang ylang, fir needle, mountain savory (winter), citronella, spearmint, elemi, vetiver, clove bud, allspice and cedarwood essential oils. The minimal inhibitory concentration (MIC) determination of these 32 top hits indicated they were not only active against stationary phase non-growing B. henselae but also had good activity against log phase growing B. henselae. The time-kill curve by drug exposure assay showed 13 active hits, including essential oils of oregano, cinnamon bark, mountain savory (winter), cinnamon leaf, geranium, clove bud, allspice, geranium bourbon, ylang ylang, citronella, elemi and vetiver, could eradicate all stationary phase B. henselae cells within 7 days at the concentration of 0.032% (v/v). Two active ingredients, carvacrol and cinnamaldehyde, of oregano and cinnamon bark essential oils, respectively, were shown to be very active against stationary phase B. henselae such that they were able to eradicate all the bacterial cells even at the concentration ≤ 0.01% (v/v). Our finding of active essential oils may help to develop more effective treatments for persistent Bartonella infections.

Preprint REVIEW | doi:10.20944/preprints202004.0299.v1

Remdesivir: A Review of Its Discovery and Development Leading to Human Clinical Trials for Treatment of COVID-19

Richard T. Eastman, Jacob S. Roth, Kyle R. Brimacombe, Anton Simeonov, Min Shen, Samarjit Patnaik, Matthew D. Hall

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; coronavirus; remdesivir

Online: 17 April 2020 (13:02:03 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202006.0233.v1

Complementary Application of the Ozonized Saline Solution in Moderate and Severe Patients with Pneumonia Covid-19: Efficacy and Tolerability

Adriana Schwartz, Gregorio Martínez-Sánchez, Alejandra Menassa de Lucía, Sergio Mejía Viana, Constanta Alina Mita

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: ozone therapy; ozonized saline solution; SARS-CoV-2; COVID-19; pneumonia

Online: 18 June 2020 (13:13:39 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202004.0165.v2

The Covid-19 Virus Double Pathogenic Mechanism. A New Perspective

Carlo Brogna

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Covid-19; Blastn; toxins protein; ACh; aChE; BuChE; CBP; Zero Point; bungaro-toxins, phospholipase A2; similar prothrombin activator protein

Online: 19 April 2020 (06:51:53 CEST)

Show abstract| Download PDF| Share

Preprint HYPOTHESIS | doi:10.20944/preprints202002.0254.v2

Discovery of Anti-2019-nCoV Agents from 38 Chinese Patent Drugs toward Respiratory Diseases via Docking Screening

Yong-Ming Yan, Xin Shen, Yong-Kai Cao, Jiao-Jiao Zhang, Yan Wang, Yong-Xian Cheng

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2019-nCoV; novel coronavirus pneumonia; docking; ACE2; viral main protease

Online: 23 February 2020 (02:09:52 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202002.0308.v1

Pharmacoinformatics and Molecular Dynamic Simulation Studies Reveal Potential Inhibitors of SARS-CoV-2 Main Protease 3CL^pro

Mubarak A. Alamri, Muhammad Tahir ul Qamar, Safar M. Alqahtani

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; 3CL protease; molecular docking; molecular dynamics and simulations

Online: 23 February 2020 (02:17:46 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202005.0020.v1

Coronavirus (2019-nCoV) Deactivation via Spike Glycoprotein Shielding by Old Drugs, Bioinformatic Study

Mohammad Reza Dayer

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; , 2019-nCoV; Heparin; Ivermectin; Spike Shielding

Online: 2 May 2020 (16:21:32 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.3390/sci1010022

Relevancy of Nizatidine Release from Floating Tablets with Viscosity of Various Cellulose Ethers

Yasser Shahzad, Namra Ibrar, Talib Hussain, Abid Mehmood Yousaf, Ikram Ullah Khan, Syed A. A. Rizvi

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: buoyancy; dissolution; floating tablets; HPMC; nizatidine; substitution level; viscosity grades

Online: 9 April 2019 (00:00:00 CEST)

Show abstract| Share

Preprint COMMUNICATION | doi:10.20944/preprints201612.0122.v1

The Food and Beverage Occurrence of Furfuryl Alcohol and β-myrcene – Two Emerging Potential Human Carcinogens?

Alex O. Okaru, Dirk W. Lachenmeier

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: furfuryl alcohol; β- myrcene; carcinogens; occurrence

Online: 25 December 2016 (08:21:19 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201712.0036.v1

The West African Sorghum Bicolor Leaf Sheath Extract Jobelyn® and Its Diverse Therapeutic Potentials

Samira Makanjuola, Olajuwon Okubena, Louis Ajonuma, Adedoyin Dosunmu, Solomon Umukoro, Patrick Erah

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Sorghum bicolor leaf extract; SBLS; Jobelyn®; antioxidant; Immune-modulatory; anti-inflammatory; anti-anemia; HIV

Online: 7 December 2017 (04:37:20 CET)

Show abstract| Download PDF| Share

Preprint COMMUNICATION | doi:10.20944/preprints202002.0418.v1

Virtual High Throughput Screening Based Prediction of Potential Drugs for COVID-19

Sekhar Talluri

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: virtual HTS; docking; drug reposition; drug repurposing; coronavirus; COVID-19; 2019-nCoV; SARS-CoV-2

Online: 28 February 2020 (02:38:05 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202003.0466.v1

The Disruption of SARS-CoV-2 RBD/ACE-2 Complex by Ubrogepant Is Mediated by Interface Hydration

Olaposi Omotuyi, Oyekanmi Nash, Bashiru Ajiboye, Damilohun Metibemu, Babatunji Oyinloye, Ayodeji Ojo, kunle Okaiyeto

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; SARS-CoV-2 RBD; Ubrogepant; ACE-2; MD simulation

Online: 31 March 2020 (22:50:27 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201609.0018.v1

Anticancer and Antioxidant Activities of Some Algae from Western Libyan Coast

Rabia Alghazeer, Mahboba Enaeli, Nazlin K. Howell

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: polyphenols, flavonoids, seaweeds, antioxidant activity, anticancer activity

Online: 5 September 2016 (14:23:52 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201701.0138.v1

Danggui-Shaoyao-San, a Traditional Chinese Medicine, Relieved Depression and Cognitive Disorder Induced by Chronic Restraint Stress Involved in Regulating Dendritic Spines Remodeling

Kecheng Zhou, Junbin Yin, Huanghui Wu, Wei Hu, Zhen Gao, Fang Li, An'an Wu, Wen Wang, Junping Kou

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Danggui-Shaoyao-San, chronic restraint stress, learning and memory, anxiety/depression, structural plasticity

Online: 31 January 2017 (15:30:41 CET)

Show abstract| Download PDF| Supplementary Files| Share

Preprint REVIEW | doi:10.20944/preprints201805.0011.v1

Changing Trends in Computational Drug Repositioning

Jaswanth K. Yella, Suryanarayana Yaddanapudi, Yunguan Wang, Anil G. Jegga

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: computational drug repositioning; drug repositioning; drug repurposing; machine learning; deep learning; crowdsourcing; open innovation; drug discovery

Online: 1 May 2018 (12:27:22 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202003.0345.v2

Widely Available Lysosome Targeting Agents Should Be Considered as a Potential Therapy for COVID-19

Jan Homolak, Ivan Kodvanj

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; lysosomotropic agents; endosome; antiviral; drug repurposing

Online: 24 March 2020 (06:26:54 CET)

Show abstract| Download PDF| Share

While the COVID-19 pandemic advances, the scientific community struggles in the search for treatments. Several improvements have been made, including the discovery of clinical efficacy of chloroquine (CQ) in COVID-19 patients, but the effective treatment protocols are still missing. In order to find novel treatment options many scientists utilize the in silico approach to identify compounds that could interfere with the key molecules involved in entrance, replication, or dissemination of the SARS-CoV-2. However, most of the identified molecules are currently not available as pharmacological agents, and assessing their safety and efficacy could take many months. Here, we took a different approach based on the proposed pharmacodynamic model of CQ in COVID-19. The main mechanism of action responsible for the favourable outcome of COVID-19 patients treated with CQ seems to be related to pH modulation-mediated effect on the endolysosomal trafficking, a characteristic of chemical compounds often called lysosomotropic agents because of the physico-chemical properties that enable them to passively diffuse through the endosomal membrane and undergo protonation-based trapping in the lumen of the acidic vesicles. In this review, we discuss lysosomotropic and lysosome targeting drugs that are already in clinical use and are characterized by good safety profiles, low cost, and wide availability. We emphasize that some of these drugs, in particular azithromycin and other macrolide antibiotics, indomethacin and some other non-steroidal anti-inflammatory drugs, proton pump inhibitors, and fluoxetine could provide additional therapeutic benefits in addition to the potential antiviral effect that still has to be confirmed by well-controlled clinical trials. As some of these drugs, mostly antibiotics, were already empirically used in the treatment of COVID-19, we encourage our colleagues all over the world to publish patient data so potential efficacy of these agents can be evaluated in the clinical context and rapidly implemented in the therapeutic protocols if the beneficial effect on clinical outcome is observed.

Preprint ARTICLE | doi:10.20944/preprints202003.0450.v1

Revealing Anti-viral Potential of Bio-active Therapeutics Targeting SARS-CoV2- polymerase (RdRp) in Combating COVID-19: Molecular Investigation on Indian Traditional Medicines

Dhanasekaran Sivaraman, Puspharaj selvadoss Pradeep

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; Indian medicines; Phytotherapeutics; Favipiravir

Online: 31 March 2020 (09:56:59 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint REVIEW | doi:10.20944/preprints202005.0295.v1

A Comprehensive Review on the Effect of Plant Metabolites on Coronaviruses: Focusing on Their Molecular Docking Score and IC50 Values

Parastou Farshi, Eda Ceren Kaya, Fataneh Hashempour-Baltork, Kianoush Khosravi-Darani

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: coronaviruses; plants metabolites; polyphenols; antiviral-effect

Online: 18 May 2020 (04:09:48 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202003.0246.v1

Association of COVID-19 Disease Severity with Transmission Routes and Suggested Changes to Community Guidelines

Jianqing Wu, Zha Ping

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: coronavirus; COVID-19; disease severity; transmission route; infection route; lung damages; cold flu influenza

Online: 15 March 2020 (14:39:19 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201609.0102.v1

Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking Induced Liver Injury

Peng Sun, Shun-Zong Song, Shuang Jiang, Xia Li, You-Li Yao, Yan-Ling Wu, Li-Hua Lian, Ji-Xing Nan

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: salidroside; inflammation; alcoholic liver injury; TLR4; TAK1

Online: 27 September 2016 (10:45:06 CEST)

Show abstract| Download PDF| Share

Working Paper HYPOTHESIS

Potential Natural Compounds for Preventing SARS-CoV-2 (2019-nCoV) Infection

Hansen Chen, Qiaohui Du

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2 (2019-nCoV); Baicalin; Scutellarin; Hesperetin; Nicotianamine; Glycyrrhizin

Online: 18 February 2020 (04:56:54 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202004.0161.v1

High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2

Birgit Strodel, Olujide Olubiyi, Maryam Olagunju, Monika Keutmann, Jennifer Loschwitz

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; SARS-CoV-2; main protease inhibition; virtual screening; drugs; natural products

Online: 9 April 2020 (14:59:37 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201704.0179.v1

Effects of Hydroalcoholic Extract of Celtis iguanaea on Markers of Cardiovascular Diseases and Glucose Metabolism in Cholesterol-Fed Rats

Barbara Zanchet, Denise B. Gomes, Vanessa S. Corralo, Kriptsan A. P. Diel, Amanda P. Schönell, Caroline Faust, Patrícia Nicola, Liz G. Muller, Ana Paula Zanatta, Silvana M. Wildner, Fernanda Bevilaqua, Rafael Chitolina, Adrieli Sachett, Leila Zanatta, Marta M. M. F. Duarte, Greicy M. M. Conterato, Claudia Q. Rocha, Camile Peretti, Tatiane Brumelhaus, Nayara Souza Alves, Jean Carlo Olivo Menegatt, Fernanda Conte, Guilherme Serena, Adriano Tony Ramos, Francielli Cordeiro Zimermann, Walter A. Roman Junior

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: medicinal plants; flavonoids; hypoglycemic; hypolipidemic; antiatherogenic

Online: 27 April 2017 (04:13:10 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202005.0199.v1

Revealing SARS-CoV-2 Functional Druggability Through Multi-Target Cadd Screening of Repurposable Drugs

Yash Gupta, Dawid Maciorowski, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Ajay Bharti, Daniel Becker, Rathi Brijesh, Steven B Bradfute, Ravi Durvasula, Prakasha Kempaiah

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; CADD; virtual screening; approved drugs; drug repurposing; essential targets; molecular docking; molecular dynamics simulations

Online: 11 May 2020 (13:14:18 CEST)

Show abstract| Download PDF| Share

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

Preprint REVIEW | doi:10.20944/preprints201803.0173.v1

The Potential Health Benefits of Noni Juice: A Review of Human Intervention Studies

Brett J. West, Shixin Deng, Fumiyuki Isami, Akemi Uwaya, C. Jarakae Jensen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Noni juice; Morinda citrifolia; clinical trial; antioxidant; immune system; inflammation

Online: 20 March 2018 (07:48:10 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201701.0044.v1

Occurrence of Aflatoxigenic Aspergillus Species in Various Varieties of Peanuts Produced in Western Kenya

Menza C. Nelson, Muturi W. Margaret, Lucy Kamau

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Aflatoxins; Peanuts; Aspergillus species

Online: 9 January 2017 (09:40:46 CET)

Show abstract| Download PDF| Share

Aflatoxin contaminates foods including peanuts. Aflatoxin is a carcinogenic toxin mainly produced bty Aspergillus flavus. Other Aspergillus species that rarely produce aflatoxins are A. nomius and A. niger. Aflatoxin is associated with liver failure, hepatocellular carcinoma (HCC) and death. Recent studies have shown that peanuts in Kenya are highly contaminated with aflatoxins but information gaps exist on the characterization of the Aspergillus species that produce aflatoxins in peanuts in Kenya. Therefore, this gap necessitated the determination of the Aspergillus species producing aflatoxins in peanuts from the main growing districts of Busia and Kisii Central districts. One hundred and two (102) peanuts samples were collected from farmers’ in each district Aspergillus species were isolated from the peanut samples by using the dilution plate technique on modified Rose Bengal agar. Phenotypical characterization of the identified Aspergillus section flavus isolates from the peanuts samples was determined using the procedure of Mellon and Cotty. This study identified five (5) Aspergillus species as contaminants in peanuts analyzed in this study. They were Aspergillus flavus L-strain, Aspergillus flavus S-strain, Aspergillus parasiticus, Aspergillus niger and Aspergillus tamari. Overall, the occurrence of Aspergillus flavus L- strain and A. flavus S- strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species identified in the study with a mean occurrence of 45.1%. Aspergillus flavus L- strain was the most common isolate (58.8%) in peanuts from Busia district while A. flavus S- strain was the most common strain (60.2%) in peanuts from Kisii Central district. Overall, the occurrence of Aspergillus flavus L strain and A. flavus S strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species (F=3.15, df =25, P=0.031) with an overall mean occurrence of 45.1%. The confirmation of occurrence of other species that produce toxins such as A. niger and A. tamarii which also produces cyclopiazonic acid suggests the need to screen peanuts for other carcinogenic mycotoxins.

Preprint ARTICLE | doi:10.20944/preprints201611.0048.v1

Uridine Triphosphate Thio-analogues Inhibit Platelet P2Y₁₂ Receptors and Aggregation

Dursun Guenduez, Christian Tanislav, Daniel Sedding, Mariana Parahuleva, Sentot Santoso, Christian Troidl, Christian Hamm, Muhammad Aslam

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2S-UTP; 4S-UTP; P2Y12 receptors; ADP; platelet aggregation

Online: 8 November 2016 (10:23:48 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201608.0011.v1

Curcumin Ameliorates Furazolidone Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells via Inhibiting ROS Production and Mitochondrial Pathway

Chongshan Dai, Daowen Li, Lijing Gong, Xilong Xiao, Shusheng Tang

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: curcumin; furazolidone; oxidative stress; DNA damage; mitochondrial pathway

Online: 2 August 2016 (05:59:38 CEST)

Show abstract| Download PDF| Share

Working Paper ARTICLE

Virtual Screening and Molecular Dynamics on Blockage of Key Drug Targets as Treatment for COVID-19 Caused by SARS-CoV-2

Ailan Huang, Xue Tang, Huimin Wu, Jun Zhang, Wanqi Wang, Zhiwei Wang, Li Song, Min-an Zhai, Lihui Zhao, Hailong Yang, Xiaohui Ma, Shuiping Zhou, Jinyong Cai

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; SARS-CoV-2; 3CLpro; PLpro; RdRp; AAK1; inhibitor; dock; molecular dynamics

Online: 15 March 2020 (02:34:14 CET)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints201612.0099.v1

Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

Tania Rescigno, Mario F. Tecce, Anna Capasso

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: aging; bioactive nutrients; dietary; nutrigenomics; Oxiinflammaging

Online: 19 December 2016 (09:37:23 CET)

Show abstract| Download PDF| Share

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.

Preprint ARTICLE | doi:10.20944/preprints201609.0006.v1

Cytotoxic Activity of Vernonia mespilifolia Less Used in the Folk Medicine in the Eastern Cape Province, South Africa

Jeremiah Oshiomame Unuofin, Gloria Aderonke Otunola, Anthony Jide Afolayan

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Vernonia mespilifolia; Artemia salina; toxicity; biological activity; hatchability; lethality

Online: 2 September 2016 (11:24:10 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201807.0224.v1

Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha

Julia Sperlich, Nicole Teusch

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: pseudopterosin; triple negative breast cancer; glucocorticoid receptor alpha; dexamethasone; cell proliferation; 3D invasion; tumor spheroid; co-culture; interleukin 6; interleukin 8

Online: 13 July 2018 (04:47:23 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints201611.0048.v2

Uridine Triphosphate Thio-analogues Inhibit Platelet P2Y₁₂ Receptors and Aggregation

Dursun Guenduez, Christian Tanislav, Daniel Sedding, Mariana Parahuleva, Sentot Santoso, Christian Troidl, Christian Hamm, Muhammad Aslam

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2S-UTP; 4S-UTP; P2Y12 receptors; ADP; platelet aggregation

Online: 28 December 2016 (10:46:04 CET)

Show abstract| Download PDF| Share

Preprint HYPOTHESIS | doi:10.20944/preprints202002.0254.v1

Discovery of Anti-2019-nCoV Agents from Chinese Patent Drugs via Docking Screening

Yong-Ming Yan, Xin Shen, Yong-Kai Cao, Jiao-Jiao Zhang, Yan Wang, Yong-Xian Cheng

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2019-nCoV; novel coronavirus pneumonia; docking; ACE2; viral main protease

Online: 18 February 2020 (03:06:39 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201612.0042.v1

Anti-inflammatory Activity of Sanghuangporus sanghuang Mycelium

Wang-Ching Lin, Jeng-Shyan Deng, Shyh-Shyun Huang, Sheng-Hua Wu, Chin-Chu Chen, Wan-Rong Lin, Hui-Yi Lin, Guan-Jhong Huang

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: acute lung injury; mycelium of Sanghuangporus sanghuang; lipopolysaccharide; KAP1/Nrf2 pathway; PI3K/Akt/mTOR pathways; HO-1; HNGB1

Online: 7 December 2016 (11:15:30 CET)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints201612.0048.v1

A Review on Phytochemistry and Pharmacology of Cortex Periplocae

Yang Li, Jin Li, Kun Zhou, Jun He, Jun Cao, Ming-Rui An, Yan-Xu Chang

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Cortex Periplocae; traditional Chinese medicines; periplocin; phytochemistry; biological activities

Online: 8 December 2016 (10:24:43 CET)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202211.0221.v3

Tucaresol: A Unique Oral Candidate Drug Ideally Accessible for Treatment of COVID-19 Disease

Christopher Penney, Boulos Zacharie, Jean-Simon Duceppe

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Tucaresol; COVID-19; SARS-CoV-2; HIV; T helper cell; CD4 receptor

Online: 14 March 2023 (08:51:05 CET)

Show abstract| Download PDF| Share

Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Preprint ARTICLE | doi:10.20944/preprints201609.0070.v1

Effects of Fetal Exposure to Asian Sand Dust on Fetal Development and Reproductive Function in Male Offspring

Seiichi Yoshida, Takamichi Ichinose, Keiichi Arashidani, Miao He, Hirohisa Takano, Takayuki Shibamoto

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: asian sand dust; in utero exposure; secondary sex ratio; male reproduction; daily sperm production

Online: 20 September 2016 (11:39:47 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints201905.0091.v1

UNaProd: A Universal Natural Product Database for Materia Medica of Iranian Traditional Medicine

Ayeh Naghizadeh, Donya Hamzeheian, Jehad Aldahdooh, Shaghayegh Akbari, Fahimeh Mohammadi, Tohid Otoufat, Saeme Asgari, Azadeh Zarei, Samane Noroozi, Najmeh Nasiri, Mahdi Salamat, Reza Karbalaei, Mehdi Mirzaie, Hossein Rezaeizadeh, Jing Tang, Mehrdad Karimi, Mohieddin Jafari

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Iranian traditional medicine; alternative and complementary medicine; database; natural products; Mizaj; temperament

Online: 8 May 2019 (10:08:54 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint REVIEW | doi:10.20944/preprints202004.0207.v1

Chinese Guidelines Related to Novel Coronavirus Pneumonia

Tingting Qiu, Shuyao Liang, Monique Dabbous, Yitong Wang, Ru Han, Mondher Toumi

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Chinese Guidelines; COVID-19; pharmaceutical treatment

Online: 13 April 2020 (03:43:37 CEST)

Show abstract| Download PDF| Share

Background and Objective: China has managed to control the coronavirus disease (COVID-19) with confinement measurements and treatment strategies, while other countries are struggling to contain the spread. This study discusses the guidelines related to COVID-19 in China in order to provide important references for other countries in the fight against COVID-19. Methods: Chinese guidelines relevant to COVID-19 were systematically searched via the China National Knowledge Infrastructure database, YiMaiTong database, and World Health Organization (WHO) COVID-19 database on March 20^th, 2020. Guideline information was extracted, including date of publication, source, objectives and the target population. Guidelines specific to the pharmacological treatment of COVID-19 were further investigated to identify the types of antivirus drugs recommended and to report on how treatment recommendations for COVID-19 have evolved overtime. Results: A total of 114 guidelines were identified, of which 87 were national guidelines and 27 were regional guidelines. The scope of included guidelines consisted of: the diagnosis and treatment of COVID-19, the management of hospital departments and specific diseases during the outbreak of COVID-19. Sixty-four of the included guidelines targeted all COVID-19 patients, while the remaining guidelines concentrated on special patient populations (i.e., geriatric population, pediatric population, and pregnant population) or patients with coexisting diseases. Twenty-three guidelines focused on the pharmacological treatments for all COVID-19 patients. Interferon, Lopinavir/Ritonavir, Ribavirin, Chloroquine, and Umifenovir represented the most recommended antivirus drugs. With the emergence of encouraging results from preclinical and preliminary clinical studies, Chloroquine Phosphate was recommended in the national Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (6^th version) on February 19^th, 2020. Thereafter, more detailed guidelines regarding the adjustment of dosage regimens and the monitoring of adverse events of Chloroquine Phosphate were published. To date, 8 Chinese guidelines have recommended Chloroquine Phosphate or Hydroxychloroquine as mainstream antivirus drug for the treatment of COVID-19. Conclusions: China has generated a plethora of guidelines covering almost all aspects of COVID-19. Chloroquine, as one widely affordable treatment, holds great potential to become the gold standard choice as more clinical evidence is shared by researchers from China as well as other countries.

Preprint REVIEW | doi:10.20944/preprints202006.0232.v1

Repurposing of FDA Approved Drugs as COVID-19 Therapeutics: Safety Concerns and Contraindications of Drugs in Clinical Trials

Ravinder Naik Dharavath, Meenu Dutt, Sunil Kumar, Priya Badyal, Nitin Rawat, Tanzeer Kaur, Shweta Sharma, Mahendra Bishnoi, Kanwaljit Chopra

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Adverse drug reactions; Anti-COVID drugs; Coronavirus; Drug repurposing; Drug toxicity; Pharmacotherapy

Online: 18 June 2020 (12:43:43 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints201909.0098.v1

Methods for Studying Endoplasmic Reticulum Stress

Daniela Correia da Silva, Patricia Valentao, Paula Andrade, David Pereira

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: unfolded protein response; endoplasmic reticulum; PERK; IRE-1; ATF4

Online: 9 September 2019 (11:54:25 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201909.0107.v1

Compatibility and Stability of Daptomycin Lock Solutions in Combination with Gentamicin, Azithromycin, Heparin and Trisodium Citrate

P. Brandon Bookstaver, Padmavathy Premnath, Kayisa Wright, Campbell McInnes

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: daptomycin; antibiotic lock therapy; gentamicin; azithromycin; catheter-related bloodstream infections

Online: 10 September 2019 (10:43:51 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201703.0237.v1

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Anti-Proliferation Effects in Hepatocellular Carcinoma Cells

Subbroto Kumar Saha, Yingfu Yin, Kyeongseok Kim, Gwang-Mo Yang, Ahmed Abdal Dayem, Hye Yeon Choi, Ssang-goo Cho

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: valproic acid; doxorubicin; reactive oxygen species; autophagy; cell death; caveolae endocytosis pathway

Online: 31 March 2017 (12:08:53 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201609.0034.v1

Antidermatophytic Activity of the Fruticose Lichen Usnea orientalis

Ashutosh Pathak, Anupam Dikshit

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: antidermatophytic; dermatophytes; DPPH; Lichen

Online: 9 September 2016 (07:44:48 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202003.0345.v1

Widely Available Lysosomotropic Agents Should Be Considered as a Potential Therapy for COVID-19

Jan Homolak, Ivan Kodvanj

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; lysosomotropic agents; endosome; antiviral; drug repurposing

Online: 23 March 2020 (07:28:51 CET)

Show abstract| Download PDF| Share

While the COVID-19 pandemic advances, the scientific community struggles in the search for treatments. Several improvements have been made, including the discovery of clinical efficacy of chloroquine (CQ) in COVID-19 patients, but the effective treatment protocols are still missing. In order to find novel treatment options many scientists utilize the in silico approach to identify compounds that could interfere with the key molecules involved in entrance, replication, or dissemination of the SARS-CoV-2. However, most of the identified molecules are currently not available as pharmacological agents, and assessing their safety and efficacy could take many months. Here, we took a different approach based on the proposed pharmacodynamic model of CQ in COVID-19. The main mechanism of action responsible for the favourable outcome of COVID-19 patients treated with CQ seems to be related to pH modulation-mediated effect on the endolysosomal trafficking, a characteristic of chemical compounds often called lysosomotropic agents because of the physico-chemical properties that enable them to passively diffuse through the endosomal membrane and undergo protonation-based trapping in the lumen of the acidic vesicles. In this review, we discuss lysosomotropic drugs that are already in clinical use and are characterized by good safety profiles, low cost, and wide availability. We emphasize that some of these drugs, in particular azithromycin and other macrolide antibiotics, indomethacin and some other non-steroidal anti-inflammatory drugs, proton pump inhibitors, and fluoxetine could provide additional therapeutic benefits in addition to the potential antiviral effect that still has to be confirmed by well-controlled clinical trials. As some of these drugs, mostly antibiotics, were already empirically used in the treatment of COVID-19, we encourage our colleagues all over the world to publish patient data so potential efficacy of lysosomotropic agents can be evaluated in the clinical context and rapidly implemented in the therapeutic protocols if the beneficial effect on clinical outcome is observed.

Preprint ARTICLE | doi:10.20944/preprints201705.0100.v1

Role of Zucchini and Its Distinctive Components in the Modulation of Degenerative Processes: Genotoxicity, Antigenotoxicity, Cytotoxicity and Apoptotic Effects

Damián Martínez-Valdivieso, Rafael Font, Zahira Fernández-Bedmar, Tania Merinas-Amo, Pedro Gómez, Ángeles Alonso-Moraga, Mercedes Del Río-Celestino

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: cancer; carotenoid; chemoprevention; Cucurbita; cytotoxicity; DNA-protection; tumor cells

Online: 11 May 2017 (17:31:47 CEST)

Show abstract| Download PDF| Share

Working Paper REVIEW

The Rationale for Potential Pharmacotherapy of COVID-19

Maha Saber-Ayad, Mohamed A. Saleh, Eman Abu-Gharbieh

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; redmdesivir; cholorquine; therapy; SARS-CoV-2

Online: 10 May 2020 (18:26:04 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202002.0198.v1

Suggestion of an Alternative Approach of Inhalation of Volatile Chemicals from Onion and Garlic for Isolated Patient of Mild Onset Infected Flu: Review and Communication

Huibing Tan, Ganqiu Wu, Xiaotong Li, Wei Hou

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: mild virus-infected flu; home-based treatment; inhalation of volatile chemicals; onion; garlic

Online: 15 February 2020 (14:38:20 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201706.0120.v1

Sinulariolide Suppresses Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase through the PI3K/AKT/mTOR Signaling Pathway in Human Bladder Cancer Cells

Yu-Jen Wu, Chih-I Liu, Zhong-Hao Din, Te-Chih Cheng, Jui-Hsin Su

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: sinulariolide; human bladder cancer; migration; invasion; PI3K/AKT/mTOR signaling pathway

Online: 27 June 2017 (06:23:44 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201708.0097.v1

A Novel Acidic Myotoxic Phospholipase A₂ of Colombian B. asper Venom. Isolation and Functional Characterization

Silvia Posada Arias, Paola Rey-Suárez, Jaime Andrés Pereáñez Jiménez, Cristian Acosta, Mauricio Rojas López, Lucilene Delazari Dos Santos, Rui Seabra Ferreira Junior, Vitelbina Núnez Rangel

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: snake venom; Bothrops asper; acidic myotoxic phospholipase A2; myotoxicity; edema

Online: 28 August 2017 (06:27:59 CEST)

Show abstract| Download PDF| Share

Working Paper ARTICLE

Complementary Application of the Ozonized Saline Solution in Mild and Severe Patients with Pneumonia Covid-19

Adriana Schwartz, Gregorio Martínez-Sánchez, Alejandra Menassa de Lucía, Sergio Mejía Viana, Constanta Alina Mita

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: ozone therapy; ozonized saline solution; SARS-CoV-2; COVID-19; pneumonia

Online: 3 July 2020 (08:46:48 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201710.0143.v1

Thiopurine Drugs Repositioned as Tyrosinase Inhibitors

Joonhyuck Choi, You-Mie Lee, Jun-Goo Jee

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: cheminformatics; docking simulation; drug repositioning; thiopurine; tyrosinase

Online: 22 October 2017 (14:03:13 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201803.0240.v1

Determination of the Content of Mercury in Vitamin and Mineral Dietary Supplements

Barbara Brodziak-Dopierała, Agnieszka Fischer, Patrycja Derkacz, Jerzy Stojko

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: vitamin and mineral dietary supplements; mercury

Online: 29 March 2018 (03:52:58 CEST)

Show abstract| Download PDF| Share

Dietary supplements are more and more often used to increase daily intake of essential vitamins and minerals. These preparations are classified as special category of foods and are subject to food law, not pharmaceutical regulations. As a result the requirements to dietary supplements are much less restrictive than to medications. Also simple and inexpensive procedure of registration causes that the number of dietary supplements is widely spread every year. On every manufacturing phases of dietary supplements, there is a risk of contamination. One of the pollutions might be mercury which is classified as heavy metal. Its inorganic compounds damage kidneys and liver and methylmercury is easily absorbed from gastrointestinal system. Methylmercury is distributed in all tissues, also in nervous system. The aim of study was to determine the level of mercury in multivitamins and multiminerals preparations and to analyze the results. The study included 22 dietary supplements containing vitamins and minerals available on Polish market. Mercury was analyzed with atomic absorption spectrometry using AMA 254. The concentrations of Hg was 0.22–5.85 µg/kg (the average content was 2.40 µg/kg). The highest average mercury content was 4.51 µg/kg, whereas the lowest one was 0.31 µg/kg. The results was also analyzed in individual groups depending on main component and indication for use as well as pharmaceutical formulation. Also according to manufacturer’s recommendation, the dose of mercury taken with a single medicine was estimated for time of a day, a week, a month, 3 months and also a year. The findings were compared to limits defined in regulations of European Union and PTWI set by JECFA to assess the health risk. The results presented in this study proved that the amount of mercury in tested dietary supplements is much lower than the value of valid regulations. Analyzed supplements as long as they are used with the recommendation of manufacturer, do not pose a threat to human health.

Preprint ARTICLE | doi:10.20944/preprints202006.0107.v2

Daily Low Dose of Erythropoietin in Neuroinflammation; EPO Might Be Hazardous in COVID-19

Reza Nejat, Ahmad Shahir Sadr, Alireza Ebrahimi, Alireza Nabati, Elham Eshaghi

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Ang II; COVID19; erythropoietin; EPO-R; neuroinflammation: AT1R; SARS-CoV2; angiotensin(1-7); COVID-19 encephalopathy

Online: 20 August 2020 (09:06:38 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201705.0120.v1

Protective Effect of Chokeberry (Aronia melanocarpa L.) Extract Against Cadmium Impact on the Biomechanical Properties of the Femur: A Study in a Rat Model of Low and Moderate Lifetime Women Exposure to this Heavy Metal

Małgorzata M. Brzóska, Alicja Roszczenko, Joanna Rogalska, Małgorzata Gałażyn-Sidorczuk, Magdalena Mężyńska

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Aronia melanocarpa berries; bone biomechanical properties; cadmium; chokeberries; female rats; polyphenols; procollagen; protection

Online: 16 May 2017 (07:45:30 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints201706.0017.v1

Evaluation of the Cardiotoxicity of Evodiamine In Vitro and In Vivo

WeiFeng Yang, Lina Ma, Sidi Li, KaiYu Cui, Lei Lei, ZuGuang Ye

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: evodiamine; primary cultured neonatal rat cardiomyocytes; zebrafish; cardiotoxicity; oxidative stress

Online: 2 June 2017 (08:07:04 CEST)

Show abstract| Download PDF| Share

Working Paper ARTICLE

Complementary Application of the Ozonized Saline Solution in Mild and Severe Patients with Pneumonia Covid-19: A Non-randomized Pilot Study

Adriana Schwartz, Gregorio Martínez-Sánchez, Alejandra Menassa de Lucía, Sergio Mejía Viana, Constanta Alina Mita

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: ozone therapy; ozonized saline solution; SARS-CoV-2; COVID-19; pneumonia

Online: 12 July 2020 (16:30:51 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints201702.0048.v2

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins

Robert Frangež, Dušan Šuput, Jordi Molgó, Evelyne Benoit

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: ostreolysin A/pleurotolysin B; equinatoxins; pore-forming proteins; biological effects

Online: 5 April 2017 (15:36:57 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201901.0250.v1

Nano PGE1 Enhances Phosphorylation of ERK1/2 and Akt to Promote Recovery from Motor Dysfunction and Muscle Atrophy Induced by Sciatic Nerve Injury

Mitsuko Takenaga, Tsutomu Ishihara, Jun Niimi, Akemi Hamaguchi, Teita Asano, Reiko Tsuchiya, Yuki Ohta, Tohru Mizushima, Kazuo Yudoh

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: drug delivery system, muscle atrophy, nanoparticle, prostaglandin E1, sciatic nerve injury

Online: 24 January 2019 (08:51:02 CET)

Show abstract| Download PDF| Supplementary Files| Share

Preprint REVIEW | doi:10.20944/preprints202005.0510.v1

Early and Contemporary Human Neuroimaging Studies of Serotonergic Psychedelics

Enzo Tagliazucchi

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: psychedelics; neuroimaging; consciousness

Online: 31 May 2020 (20:53:59 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201706.0126.v1

2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway

Jeong-Hyeon Ko, Jae Hwi Lee, Sang Hoon Jung, Seok-Geun Lee, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Woong Mo Yang, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2,5-Dihydroxyacetophenone; multiple myeloma; MAPK; apoptosis

Online: 29 June 2017 (08:40:36 CEST)

Show abstract| Download PDF| Share

Preprint COMMUNICATION | doi:10.20944/preprints201804.0334.v1

What Temperature of Coffee Exceeds the Pain Threshold? Organoleptical Methodology as Basis for Cancer Risk Assessment Including Feasibility Study

Julia Dirler, Gertrud Winkler, Dirk W. Lachenmeier

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: coffee; temperature; esophageal cancer; thermosensing; sensory thresholds; methodological study

Online: 26 April 2018 (08:05:50 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201703.0132.v1

High-Performance Prediction of Agonists on Human Estrogen Receptor Based on Chemical Structures

Yuki Asako, Yoshihiro Uesawa

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: machine learning; random forest; estrogen receptor; Tox21 data challenge 2014; QSAR prediction model

Online: 17 March 2017 (04:49:28 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201902.0116.v1

GC-MS Based Metabolomics to Evaluate Three Commercial Products of Chrysanthemun morifolium Hang-ju in Different Flowering and Processing Stages

Dandan Wei, Xiangwei Chang, Yaqi Cao, Hui Yan, Erxin Shang, Dawei Qian, Xiaodong Sun, Jin-ao Duan

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Flos chrysanthemum; Bud Chrysanthemum; Fetal Chrysanthemum; Hongxinju; GC-MS based metabolomics; violate components

Online: 13 February 2019 (13:08:09 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201708.0024.v1

Sub-Chronic Toxicity Study of Hydroethanolic Leaf Extract of Telfairia Occidentalis Hook. F. (Cucurbitaceae) in Rats

Abidemi J. Akindele, Joy A. Oladimeji-Salami, Ramon A. Oyetola, Daniel D. Osiagwu

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Telfairia occidentalis; Cucurbitaceae; subchronic; toxicity; biochemical; haematological

Online: 7 August 2017 (16:00:43 CEST)

Show abstract| Download PDF| Share

Background: The leaf of Telfairia occidentalis Hook f. (Cucurbitaceae) is consumed in different parts of Nigeria because of the numerous nutritional and medicinal attributes ascribed to it. The sub-chronic toxicity of the hydroethanolic leaf extract of Telfairia occidentalis (TO) was investigated in this study. Methods: Rats in different groups were separately administered 80, 400 and 2000 mg/kg TO p.o. for 60 days. Animals were sacrificed and blood samples collected for haematological and biochemical analysis. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: Results showed no significant changes in the weight of vital organs except in respect of the testes of the group treated with 2000 mg/kg extract which showed a significant (p<0.05) reduction in weight compared to the control group. There was a significant (p<0.01) increase in sperm motility and count of the group administered 80 mg/kg extract and a significant (p<0.001) reduction was observed at 2000 mg/kg. There were significant increases in the level of Hb and PCV at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, a significant decrease in AST and ALT levels at doses of 400 and 2000 mg/kg relative to control was observed. A significant reduction (p<0.05) in the level of total cholesterol (400 mg/kg) and increase (p<0.05) in level of HDL (80-2000 mg/kg) compared to control was observed. There was also significant (p<0.05) increase in the level of MDA and significant (p<0.05) decrease in SOD level in the testes at 2000 mg/kg. Histopathological assessment of the testes revealed abnormality at this dose. These effects were reversed after 30 days of cessation of administration of TO. Conclusions: The findings showed that the hydroethanolic leaf extract of Telfairia occidentalis is relatively non-toxic on acute and sub-chronic exposure, with potential to elicit anti-anaemic effect, reduce the risk of atherosclerosis and cardiovascular disease, and enhance antioxidant status in the brain and liver. Although possibly beneficial at low dose, the extract could be harmful to the testes on prolonged oral exposure at high dose.

Preprint ARTICLE | doi:10.20944/preprints201709.0086.v1

Praeruptorin A Inhibits Cervical Cancer HeLa Cell Growth and Invasion by Suppressing MMP-2 Expression and ERK1/2 Signaling

Min-Hua Wu, Chia-Liang Lin, Hui-Ling Chiou, Shun-Fa Yang, Yi-Hsien Hsieh, Chung-Jung Liu

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: praeruptorin A; human cervical cancer; ERK; Invasion; MMP-2; TIMP-2

Online: 19 September 2017 (07:45:00 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201708.0060.v1

Glycemic Regulation and Cytotoxic Characteristics of the Ethyl Acetate Fraction from Passiflora cincinnata Mast Leaves

Charles dos Santos Estrevam, Clésio Andrade Lima, Jymmys Lopes dos Santos, Murilo Marchioro, Brancilene Santos Araujo, Cristiane Bani Corrêa, Camila M.C Santos, Iara Samir Santana, Silvan Silva Araújo

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Passiflora cincinnata Mast; redox activity; cell cytotoxicity; α-amylase inhibition; antihyperglycaemic

Online: 17 August 2017 (10:29:55 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201709.0070.v1

Versatility of 7-Substituted Coumarin Molecules as Antimycobacterial Agents, Neuronal Enzyme Inhibitors and Neuroprotective Agents

Erika Kapp, Hanri Visser, Samantha L. Sampson, Sarel F. Malan, Elizabeth M. Streicher, Germaine B. Foka, Digby F. Warner, Sylvester L. Omoruyi, Adaze B. Enogieru, Okobi E. Ekpo, Frank T. Zindo, Jacques Joubert

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Coumarin; Mycobacterium tuberculosis; Cholinesterase inhibitor; Monoamine oxidase B inhibitor; Structure activity relationship; Albumin binding, Neuroprotection

Online: 15 September 2017 (17:34:38 CEST)

Show abstract| Download PDF| Share

Preprint HYPOTHESIS | doi:10.20944/preprints202005.0061.v1

Lysosomotropic Active Compounds—Hidden Protection against COVID-19 / SARS-CoV-2 Infection?

Markus Blaess, Lars Kaiser, Martin Sauer, Hans-Peter Deigner

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; Lysosomotropism; Chloroquine

Online: 5 May 2020 (04:29:48 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201906.0119.v1

Utilization of Antibiotic Prophylaxis in Three Common Abdominal Surgeries, Adherence to Standard Guidelines and Surgeons' Perception in Teaching Hospitals, Islamabad, Pakistan

Zakir Khan, Naveed Ahmed, Asim ur Rehman, Faiz ullah Khan, Hazir Rahman

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: audit; utilization; surgery; antibiotics; perception; infections; hospitals

Online: 13 June 2019 (09:52:04 CEST)

Show abstract| Download PDF| Share

Background and objectives: The appropriate use of antibiotics is the main strategy of Antimicrobial stewardship program. This study was planned to evaluate the quality of antibiotic prescriptions, its adherence with standard guidelines and surgeons’ perception regarding antibiotic use in surgeries. Methods: A prospective cross-sectional observational and survey-based study comprised of two sections: Phase 1; to investigate the antibiotic utilization in three most common abdominal surgical procedures during 9 months (January 2017 to September 2017). The appropriateness of antibiotics was compared with evidence-based guidelines. Phase 2; the surgeon’s perspectives were evaluated through a self-administered questionnaire (13 items) during the next three months (October 2017 to December 2017). Descriptive statistics, chi-square and Fisher’s exact tests analysis were used through SPSS Statistical Package 21.0. Results: A total of 866 eligible surgical cases out of 1015 were investigated. An acute appendectomy (n= 418; 48.2%) was most common surgical intervention followed by laparoscopic cholecystectomy (n= 278; 32.1%) and inguinal hernia (n= 170; 19.7%). About 97.5% of patients received antibiotics. Among these, 9.5% adhered according to guidelines with respect to correct choice, 40% for timing, 100% for dose and route (optimal value 100%). The ceftriaxone (J01XD04; n= 503; 59.5%) was most frequently prescribed antibiotic. A 200 participants (response rate 70.6%) filled out a validated questionnaire (internal consistency; α ≥ 0.7). One hundred and thirty-eight (69%) reported the overuse of antibiotics and most of them (97%) preferred broad-spectrum antibiotics instead of narrow-spectrum. The participants reported that non-availability hospital-based guidelines (n=193; 96.5%), prescribing of antibiotics without guidelines (n=186; 93%), underestimation of infection (n=177; 88.5%), lack of consensus (n=135; 67.5%) and poor awareness about guidelines (n=122; 61%) were the main determinants in their health care settings. Conclusions: The compliance of Surgical antibiotic was far below the recommendations of guidelines. The urgent needs of awareness among surgeons and implementation of antimicrobial stewardship program were important recommended interventions for appropriate use antibiotics.

Preprint ARTICLE | doi:10.20944/preprints201801.0271.v1

Anti-Proliferation, Pro-Apoptosis and Anti-Migration Effects of Ginkgolic Acid C13:0 Isolated from Ginkgo Biloba Exocarp in MCF-7 and 4T-1 Breast Cancer Cells

Da-Yu Zhou , Chun-Ying Jiang, Cheng-Hao Fu, Ping Chang, Jia-Di Wu, Ke-Xin Zheng, Xiao-Hui Zhao, Shi-Liang Ma

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: breast cancer; ginkgolic acid C13:0; mechanism; CYP1B1

Online: 29 January 2018 (09:57:10 CET)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints201808.0435.v1

Antibiotic Resistance Pattern of Bacteria Isolated from patients with upper respiratory tract infections; a four year study in Tripoli city

Ahmed Atia, Najla Elyounsi, Ahmed Abired, Amal Wanis, Abdulsalam Ashour

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Respiratory tract infections (RTI); antibiotic; sensitivity; resistant; bacteria

Online: 24 August 2018 (11:46:41 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202004.0015.v2

Computational Screening of Molecules Approved in Phase-I Clinical Trials to Identify 3CL Protease Inhibitors to Treat COVID-19

Kamlesh Sahu, Sergei Noskov, Jack Tuszynski, Michael Houghton, D. Lorne Tyrrell

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: virtual screening; COVID-19; Protease 3CL pro

Online: 3 April 2020 (15:08:50 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201711.0062.v1

Sacubitril-Valsartan for Heart Failure with Reduced Left Ventricular Ejection Fraction: A Retrospective Study

Renato De Vecchis, Carmelina Ariano

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: sacubitril valsartan; heart failure; treatment

Online: 9 November 2017 (09:17:37 CET)

Show abstract| Download PDF| Share

Introduction In sacubitril-valsartan (sacub/v), the effects of an angiotensin II receptor blocker (ARB) exerted by valsartan are strengthened by the addition of sacubitril, an inhibitor of neutral endopeptidases. PARADIGM - HF study proved this association to be superior to enalapril in reducing both all-cause death and cardiovascular mortality, as well as heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction( HFREF) belonging to NYHA class II-IV. To test whether even in our experience sacub/v is associated with favorable outcomes concerning mortality and morbidity, an outpatient small population of HFREF patients was retrospectively studied, of whom one third was treated with sacub/v instead of conventional therapy with ACE -inhibitors or ARBs. Methods A retrospective cohort study was carried out to assess the effects of sacub/v in addition to beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients in NYHA classes II-III compared with conventional therapy (comprising ACE inhibitor or ARB added to beta-blocker plus a MRA) administered in a second group of HFREF patients with comparable clinical features retrospectively enrolled as controls. In the two groups, the therapeutic regimen was established in accordance with the preferences of the treating physician. Additionally, in both groups, evidence-based drug therapy was supplemented by the adjunct of a loop diuretic, usually furosemide, at variable doses. The primary outcomes of interest were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia and worsening renal function. Results Mortality at six months was 6.8% in patients under therapy with sacub/v versus 34% in those treated with conventional therapy (odds ratio[OR] = 0.14; 95% CI: 0.04-0.49). Moreover, HF hospitalizations in the observation period considered were 4.5% in sacub/v group versus 59% in the conventional therapy group (OR = 0.03; 95% CI: 0.01–0.14). Safety outcomes included in our study (angioedema, hyperkalemia, hypotension and worsening renal function) showed a comparable profile in the two groups, with evidence of good tolerability of sacub/v , except for the side - effect " hypotension" (PAS < 100 mm Hg) , found in 15.9% of patients under sacub/v versus 5.7% reported in controls (OR = 3.14; 95% CI: 0.94–10.55). Conclusions In our experience, sacub/v has yielded a strong protection against both all-cause death and HF hospitalizations at six months , in the absence of significant noxious side effects. Nevertheless, considering the retrospective character of the study and the relatively exiguous sample size, further post marketing observational studies would be desirable . In particular, studies aiming at exploring safety of the new pharmacologic principle, namely mainly focusing on hypotension and angioedema, are warranted, in order to validate further this very efficacious molecule for therapy of chronic HF, especially stable HFREF in NYHA classes II-III.

Preprint ARTICLE | doi:10.20944/preprints201807.0527.v1

GLP-1 Analogue Liraglutide Attenuates Mutant Huntingtin-Induced Neurotoxicity by Restoration of Neuronal Insulin Signaling

Ching-Chi Chang, Tzu-Chin Lin, Hsiao-Li Ho, Chien-Yin Kuo, Hsin-Hua Li, Tatiana A. Korolenko, Wei-Jen Chen, Te-Jen Lai, Ying-Jui Ho, Chih-Li Lin

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: autophagy; huntingtin; insulin signaling; liraglutide; oxidative stress

Online: 27 July 2018 (03:35:44 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202007.0519.v1

Plant Mediated Green Synthesis of Zinc Oxide Nanoparticles for Burn Wound Therapy

Mohd Riyaz Beg, Shital Ghodinde, Vidhi Gupta

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Burn wounds; ZnO NPs; Plant-based Green Synthesis; Wound healing

Online: 22 July 2020 (11:10:15 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201801.0134.v1

Three Bufadienolides-Induced Human Lung Cancer CL1-5 Cell Death Mainly through Autophagy

Hui-Chi Huang, Meng-Shiou Lee, Wen-Te Chang, Hsing-Yu Chen, Yu-Hua Chen, Chi-Chen Lin, Ming-Kuem Lin

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Kalanchoe tubiflora; bufadienolide; CL1-5 human lung cancer cells; autophagy

Online: 16 January 2018 (06:38:11 CET)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints201702.0048.v1

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins

Robert Frangež, Dušan Šuput, Jordi Molgὀ, Evelyne Benoit

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: ostreolysin A/pleurotolysin B; equinatoxins; pore-forming proteins; biological effects

Online: 14 February 2017 (08:56:12 CET)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints201910.0216.v1

Antivenin Plants Used for Treatment of Snakebites in Uganda: Ethnobotanical Reports and Pharmacological Evidences

Timothy Omara, Sarah Kagoya, Abraham Openy, Tom Omute, Stephen Ssebulime, Kibet Mohamed Kiplagat, Ocident Bongomin

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: antiophidic; antivenin plants; envenomation; ethnobotany; ethnomedicine; phospholipase A2; snakebite; traditional medicine; Uganda

Online: 18 October 2019 (11:41:08 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Snakebite envenomation, cognized as a neglected tropical disease, is a dread public health concern with the most susceptible groups being herdsmen, the elderly, active farmers, hunters, fishers, firewood collectors, 10 to 14-year old working children and individuals with limited access to education and health care. Snakebites are fragmentarily documented in Uganda primarily because most occur in rural settings where traditional therapists end up being the first line defence for treatment. Ethnobotanical surveys in Uganda have unveiled that some plants are used to antagonize the activity of various snake venoms. This review was sought to compile the sporadic information on the vegetal species reported as antivenins in Uganda. Electronic data indicate that no study entirely reported on antivenin plants in Uganda. A total of 77 plant species belonging to 65 genera, distributed among 42 botanical families claimed as antiophidic in Uganda are used for treatment of snakebites. Majority of these species belong to family Fabaceae (30.9%), Euphorbiaceae (14.3%), Asteraceae (11.9%), Amaryllidaceae (9.5%) and Solanaceae (9.5%). The antiophidic species listed are shrubs (40.5%), trees (32.9%) and herbs (17.7%), usually found in the wild and uncultivated. Antivenin extracts are primarily prepared from roots and leaves, through decoctions, infusions, powders and juices and administered orally or topically. The most frequently encountered therapeutically important species are Allium cepa L., Carica papaya L., Securidaca longipedunculata Fres., Harrisonia abyssinica Oliv. and Nicotiana tabacum L. Baseline epidemiological data on snake envenomation and antivenin plants in Uganda remain incomplete due to inadequate research and diverse ethnic groups in the country. There is a dire need to isolate and characterize the bioactive compounds in the claimed plants to enable their adroit utilization in handling the plague of snake envenomation. More baseline data should be collected on snake ecology and human behaviour as well as antivenin plants in Uganda. Indigenous knowledge on the use of plant preparations in traditional medicine in Uganda is humongous, but if this is not quickly researched and appropriately documented, indications as to the usefulness of this vegetal treasure house will be lost in the not so distant future.

Medicine and Pharmacology