The COVID-19 pandemic has expanded globally and caused serious consequence in both health system and the economy. MPV is one of two oral antivirals for COVID-19 with mild-to-moderate symptoms that have received FDA approval so far. This study aims to evaluate the cost-utility of using MPV in COVID-19 treatment. To compare the utility costs of MPV and non-MPV treatments for COVID-19 patients, we used a decision tree model. Data on clinical efficacy, cost, and quality of life were gathered from previous studies. The incremental effective cost ratio (ICER) calculated based on costs incurred and quality-adjusted life years (QALY), was considered as primary out-come. The total cost of MPV treatment and not using MPV was 15,362,516 VND (618 USD) and 15,771,262 VND (634 USD), respectively. The estimated QALY with using-MPV was 28.33, while without MPV was 19.72. The ICER was dominant, resulting in savings of 47,453 VND/QALY (1.9 USD). MPV is a cost-effective medication used to treat COVID-19. In mild-to-moderate COVID-19 patients, MPV considerably lowers costs and improves quality of life. However, several clinical factors of the drug still need to be taken into account.

Abstract: Background: Patients with diabetes are particularly susceptible to COVID-19 infection, which can result in severe respiratory illness. Methods: This study conducted a comparative as-sessment of the impact of antiviral therapy using molnupiravir and favipiravir in COVID-19 pa-tients with underlying diabetes. A cohort of one hundred individuals infected with SARS-CoV-2, diagnosed with diabetes, and consecutively admitted, was included in the present study. These patients were treated with antivirals according to local guidelines: Group F (51 cases) was treated with favipiravir – 10 days and Group M (49 cases) was treated with molnupiravir – 5 days. Re-sults: In Group F, the average hospitalization was higher than in Group M (11.29±2.27 vs. 7.14±3.16, p

Background: COVID-19 represents a threat for frailty patients. Objective: Investigate efficacy, safety and economic value of treatment with Molnupiravir in a cohort of fragile patients affected by COVID-19. Methods: Observational, prospective study. The data collected allowed to assess efficacy and safety of Molnupiravir in real life, compare the results with a subgroup of patients treated with Nirmatrelvir-Ritonavir and to effect a cost-effectiveness analysis. Results: In January-December 2022, 435 patients (225 males, 220 females; median age 72 years), were enrolled; 24 patients were unvaccinated, 280 patients had ≥2 risk factors. Molnupiravir appeared to give better results than the SOC both clinically and economically. In these patients in comparison with literature data or SOC, hospitalization was 2.5% vs 6.8% (p<0.005), overall adverse effects 14,3% vs 30.4% (p<0.0001), severe adverse effects 2.6 vs 6.9% (p<0.001), thus involving a potential total savings of about € 92.954 per patient (8% of standard of care cost). Conclusions: early Molnupiravir treatment helped fragile patients who partially responded to vaccine, or with absolute contraindications to vaccination, to overcome COVID-19 without the need of hospitalization. Molnupiravir represents a clinical and economic effective treatment, avoiding disease progression in old patients suffering from multiple pathologies and taking several drugs.

Molnupiravir, a prodrug known for its broad antiviral activity, demonstrated efficacy in animal models of Covid-19, prompting clinical trials where initial results indicated a significant effect against the disease. However, subsequent clinical studies did not confirm these findings, leading to the rejection of molnupiravir for permanent market authorization in many countries. This report critically assessed 19 studies published in 17 reports that investigated the efficacy of molnupiravir in animal models of Covid-19 with the purpose of determining how well the design of these models informed human studies. We found that the administered doses of molnupiravir in most studies involving animal Covid-19 models were disproportionately higher than the dose rec-ommended for human use. Specifically, when adjusted for body surface area, half of the doses of molnupiravir used in the animal studies were more than twice as high as the human dose. Addi-tionally, the drug was frequently given prophylactically or shortly after SARS-CoV-2 inoculation in these models, in contrast to clinical trials where such timing is not consistently achieved. Furthermore, the recommended five-day treatment duration for humans was exceeded in several animal studies. Collectively, we suggest that these design elements in the reported animal studies contributed to a bias favoring molnupiravir, and thus inflated expectations for its efficacy against Covid-19. Addressing these elements may offer avenues to enhance the clinical efficacy of mol-nupiravir for treatment of Covid-19 that include dose increment, early treatment, and admin-istration by inhalation along with use of molnupiravir in antiviral combination therapy.

A new green-validated and highly sensitive electrochemical method for the determination of molnupiavir (MOV) has been developed using cyclic voltammetry. The proposed analytical platform involves the use of disposable screen-printed reduced graphene oxide 2.5% electrode (SPrGOE 2.5%) for the first time to measure MOV with high specificity. The surface morphology of the sensor was investigated by using a scanning electron microscope armed with an energy-dispersive X-ray probe. The fabricated sensor attains improved sensitivity when sodium dodecyl sulfate (SDS) surfactant was added to the supporting electrolyte solution. Thus, various factors were investigated in order to select the best supporting electrolyte for voltammetric determination of MOV, and the optimum conditions were achieved by employing 0.04 M Britton-Robinson at pH 2, 10-4 M SDS, and SPrGOE 2.5%. Well-defined MOV oxidation peaks were obtained with no reduction peaks in cyclic voltammetry using diffusion-controlled pathways. The method was validated using differential pulse voltammetry according to ICH guidelines, providing it to be precise, accurate, specific, and robust with linearity over a concentration range of 50-6017 ng/mL. The incorporation of the reduced graphene nanoparticles supported the in situ interaction between electrode surface and MOV, improved the selectivity, and reduced the detection limit to the concentration level of 15.98 ng/mL. The stability investigation demonstrated that SPrGOE 2.5% can provide high-stability behavior throughout a three-month period under refrigeration. The fabricated SPrGOE 2.5% was successfully employed for the measurement of MOV in pharmaceutical capsules and human bio-fluids without the interference of endogenous matrix components as well as the commonly used excipient.

Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic, however, the need for orally available antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. Methods: The SARS-CoV-2 strains 20A.EU, BA.1 and BA.2 were used to infect Vero E6 in presence of antiviral compounds alone or in combinations using 5 two-fold serial dilution of compound concentrations ≤EC90. After 48 and 72 h post-infection, viability was performed using MTT reduction assay. Supernatants were collected for plaque-assay titration. All experiments were conducted three times and in triplicate. The synergistic score was calculated using Synergy Finder version 2. Results: All compounds reached micromolar EC90. Molnupiravir and GC376 showed a synergistic activity at 48 h with an HSA score of 19.33 (p<0.0001) and an additive activity at 72 h with an HSA score of 8.61 (p<0.0001). Molnupiravir and nirmatrelvir showed a synergistic activity both at 48 h and 72 h with an HSA score of 14.2 (p=0.01) and 13.08 (p<0.0001), respectively. Conclusion: Molnupiravir associated with one of the two protease-inhibitors nirmatrelvir and GC376 showed good additive-synergic activity in vitro.

Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from 40 individuals treated with bamlanivimab/etesevimab (BAM/ETE), casirivimab/imdevimab (CAS/IMD) and sotrovimab (SOT) as well as the activity of remdesivir, nirmatrelvir and molnupiravir. mAbs and drug activity were defined as the serum dilution (ID50) and drug concentration (IC50), respectively, showing 50% protection of virus-induced cytopathic effect. All pre-infusion sera were negative for SARS-CoV-2 neutralizing activity. BAM/ETE, CAS/IMD and SOT showed activity against the WT (ID50 6,295 [4,355-8,075] for BAM/ETE; 18,214 [16,248-21,365] for CAS/IMD and 456 [265-592] for SOT) and the delta (14,780 [ID50 10,905-21,020] for BAM/ETE, 63,937 [47,211-79,971] for CAS/IMD and 1,103 [843-1,334] for SOT). Notably, only SOT was active against BA.1 (ID50 200 [37-233]) while BA.2 was neutralized by CAS/IMD (ID50 174 [134-209] ID50) and SOT (ID50 20 [9-31] ID50) but not by BAM/ETE. No significant inter-variant IC50 differences were observed for molnupiravir (1.5±0.1/1.5±0.7/1.0±0.5/0.8±0.01 μM for WT/delta/BA.1/BA.2, respectively); nirmatrelvir (0.05±0.02/0.06±0.01/0.04±0.02/0.04±0.01 μM) and remdesivir (0.08±0.04/0.11±0.08/0.05±0.04/0.08±0.01 μM). Continued evolution of SARS-CoV-2 requires updating the mAbs arsenal, however antivirals have so far remained unaffected.