Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 30 April 2020 / Approved: 2 May 2020 / Online: 2 May 2020 (16:21:32 CEST)

How to cite: Dayer, M.R. Coronavirus (2019-nCoV) Deactivation via Spike Glycoprotein Shielding by Old Drugs, Bioinformatic Study. Preprints 2020, 2020050020 (doi: 10.20944/preprints202005.0020.v1). Dayer, M.R. Coronavirus (2019-nCoV) Deactivation via Spike Glycoprotein Shielding by Old Drugs, Bioinformatic Study. Preprints 2020, 2020050020 (doi: 10.20944/preprints202005.0020.v1).

Abstract

The disease of COVID-19 comprises the most serious against human health worldwide with a high rate of virulence and mortality. The disease is caused by the 2019-nCoV virus from the beta coronavirus family. The virus makes use of its surface glycoprotein named S protein or spike to enter the human cells. The virus attached to its receptor named angiotensin-converting enzyme 2 on host cells surface via its receptor-binding domain and its fusion is mediated by cleavage at S2' site that is carried out by surface protease. Vaccines or drugs interfering with S protein binding or cleavage sites could be considered as drugs to get rid of the infection. In the current work and though docking and molecular dynamic experiments we have checked more than 100 drugs with high enough molecular weights for their shielding potency toward S protein binding sites and processing S2' sites. Our results indicate the shielding potency of: fidaxomicin > ivermectin > heparin > azithromycin > clarithromycin > eryhthromycin > niclosamide > ritonavir. Considering affluent reports regarding the complex disturbance in the immune system and multi-organ involvement in the disease there is no single or binary drug regime for cure expectedly and instead, we claim the multi-drug regime should be the choice in this context. Accordingly, we suggest our extracted drugs as an adjuvant for clinical trials.

Subject Areas

COVID-19; , 2019-nCoV; Heparin; Ivermectin; Spike Shielding

Comments (4)

Comment 1
Received: 5 May 2020
Commenter: Masashi Ohe
The commenter has declared there is no conflict of interests.
Comment: Lately, the anti-viral effects of MAC have attracted considerable attention.In this report, using structure-based drug selection, Dayer found the candidates of interfering with S protein binding or cleavage sites of SARS-CoV-2. The candidates include macrolide (MAC) such as azithromycin (AZM), clarithromycin (CAM), and erythromycin (EM). In the previous report, using structure-based drug selection for identification of SARS-CoV-2 protease inhibitors, MACs such as EM and CAM were predicted to be effective for COVID-19 (1). In fact, hydroxychloroquine (HCQ) in combination with AZM treatment was reported to be effective for COVID-19 (2). Similarly, Millan-Onate reported a case of successful recovery of COVID-19 pneumonia in a patient from Colombia after receiving chloroquine and CAM (3). Using internet, AZM in combination with HCQ treatment is carried out in French, US, and Canada. At the same time, EM in combination with HCQ treatment is carried out in Uganda, US, and Pakistan. Nowadays, clinical studies regarding MACs in combination with other drugs treatments are starting. Based on these facts, Dayer’s prediction of efficacy of MACs on SARS-CoV-2 is of great significance. 1. Dayer MR. Old drugs for newly emerging viral disease, COVID-19: Bioinformatic Prospective. arXiv: 2003.04524, 2020-arxiv.org 2. Gautret P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;20:105949. doi: 10.1016/j.ijantimicag.2020.105949. 3. Millan-Onate J, et al. Successful recovery of COVID-19 pneumonia in a patient from Colombia after receiving chloroquine and clarithromycin. Ann Clin microbial Antimicrob http://doi.org//10.118/s12941-020-oo358-y
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Comment 2
Received: 6 May 2020
Commenter: Mohammad Reza Dayer (Click to see Publons profile: )
The commenter has declared there is no conflict of interests.
Comment: Many thanks to valuable comments of Professor Masashi Ohe, indeed macrolides (MACs) in addition to their antibiotic and immunomodulatory effects and as per my bioinformatic experience they wonderfully act as an interfering candidate on SARS-CoV-2 proteins of protease and spike as well as on different receptors involved in COVID-19 complications when contrasted to other studied antibiotics in this context. Accordingly and in confirmation to Professor Masashi Ohe statement, I think MAC of azithromycin, clarithromycin, or erythromycin in conjunction with a spike shielder (as ivermectin), an antiprotease and cytokine storm blocker (as ACTEMRA) will be the better choice for COVID-19 treatment.
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Comment 3
Received: 9 May 2020
Commenter: Mohammad Reza Dayer (Click to see Publons profile: )
The commenter has declared there is no conflict of interests.
Comment: This is the private feedback I received from Francisco (https://www.researchgate.net/profile/Francisco_Barrantes2) regarding my paper, I forwarded here for more discussion by readers and in the next post I will send my reply
Hi, Mohammad
It's an interesting paper. I also conclude from my analysis that the best approach is a combination of existing drugs while we wait for the development of a vaccine.
Perhaps you should try not simply rank the ligands on the basis of pure in silico thermodynamic parameters but also to combine it with the information coming from the biomedical field. Which drugs appear to ameliorate the complications of COVID-19 in hospitalized patients? There should be good experience in your country. Are you in touch with doctors currently engaged in intensive care of COVID-19 patients?
Best of luck
Francisco
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Response 1 to Comment 3
Received: 11 May 2020
Commenter: Mohammad Reza Dayer (Click to see Publons profile: )
The commenter has declared there is no conflict of interests.
Comment: Hi, Francisco
Thank you very much for your nice and professional feedback on my paper. Though vaccine preparation is the best way for preventive purposes, it seems not useful for the treatment of affected patients by COVID-19 infection. Accordingly, I think combined regimes should be considered wisely for different viral diseases including enzyme inhibitors, spike interfering, and immune system modulatory drugs, and the COVID-19 outbreak seems to be the best opportunity for such collaboration and consensus. Surely, a combination of bioinformatic results with biomedical experience is more leading in such studies but as you well now the in vivo studies are time-consuming issues and I think that fast exchange of findings merits more priority in this context. However, I have three collaborating clinical trials on suggested drugs in my recent publications and we are waiting for the results.
Best Regards
Mohammad Reza

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