The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a major worldwide public health threat and economic burden. The pandemic is still ongoing and the SARS-CoV-2 variants are still emerging constantly, resulting in an urgent demand for new drugs to treat this disease. Molnupiravir, a biological prodrug of NHC (β-D-N(4)-hydroxycytidine), is a novel nucleoside analogue with a broad-spectrum antiviral activity against SARS-CoV, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), influenza virus, respiratory syncytial virus (RSV), bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV) and Ebola virus (EBOV). Molnupiravir showed potent therapeutic and prophylactic activity against multiple coronaviruses including SARS-CoV-2, SARS-CoV, and MERS-CoV in animal models. In clinical trials, molnupiravir showed beneficial effects for mild to moderate COVID-19 patients with a favorable safety profile. The oral bioavailability and potent antiviral activity of molnupiravir highlight its potential utility as a therapeutic candidate against COVID-19. This review presents the research progress of molnupiravir starting with its discovery and synthesis, broad-spectrum antiviral effects, and antiviral mechanism. In addition, the preclinical studies, antiviral resistance, clinical trials, safety, and drug tolerability of molnupiravir are also summarized and discussed, aiming to expand our knowledge on molnupiravir and better deal with the COVID-19 epidemic.

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3 Merck. Merck and Ridgeback's investigational oral antiviral molnupiravir reduced the risk of hospitalisation or death by approximately 50 percent compared to placebo for patients with mild or moderate COVID-19 in positive interim analysis of phase 3 study. Oct 1, 2021. https://www.merck.com/news/merck-andridgebacks-investigational-oral-antiviralmolnupiravir-reduced-the-risk-ofhospitalization-or-death-by-approximately-50percent-compared-to-placebo-for-patientswith-mild-or-moderat/ (accessed Oct 1, 2021). 4 Sheahan TP, Sims AC, Zhou S, et al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice.

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The global pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), places a heavy burden on global public health. Four SARS-CoV-2 variants of concern including B.1.1.7, B.1.351, B.1.617.2, and P.1, and two variants of interest including C.37 and B.1.621 have been reported to have potential immune escape, and one or more mutations endow them with worrisome epidemiologic, immunologic, or pathogenic characteristics. This review introduces the latest research progress on SARS-CoV-2 variants of interest and concern, key mutation sites, and their effects on virus infectivity, mortality, and immune escape. Moreover, we compared the effects of various clinical SARS-CoV-2 vaccines and convalescent sera on epidemic variants, and evaluated the neutralizing capability of several antibodies on epidemic variants. In the end, SARS-CoV-2 evolution strategies in different transmission stages, the impact of different vaccination strategies on SARS-CoV-2 immune escape, antibody therapy strategies and COVID-19 epidemic control prospects are discussed. This review will provide a systematic and comprehensive understanding of the secret of SARS-CoV-2 variants of interest/concern and immune escape.