![]() ![]() ![]() The virus genome encodes 2 cysteine proteases, a papain-like protease (PLpro), or nsp3, and a 3C-like protease (3CLpro), or nsp5. 12, 13 The SARS-CoV-2 genomic RNA includes two major open reading frames (ORFs), ORF1a and ORF1b, encompassing two-thirds of the genome and translated to pp1a and pp1b proteins. 12 The genome size of SARS-CoV-2, which was sequenced recently, is ~29.9 kb, sharing ~78% sequence homology with SARS-CoV. SARS-CoV-2 is a single-stranded, positive-sense RNA (+ssRNA) virus, which belongs to lineage B of the genus Beta-coronavirus in the Coronaviridae family. 6, 7 The COVID-19 outbreak is the third new acute infectious coronavirus disease to arise in the past two decades, following severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), 8, 9, 10, 11 indicating that coronaviruses remain a powerful threat to public health. 5 More recently, researchers found evidence of gastrointestinal manifestations and potential fecal-oral transmission of COVID-19. Severe cases are reported to show sepsis, secondary infections, and organ failure. Current studies reveal that the most common manifestations of COVID-19 are respiratory symptoms, such as fever, dry cough, and even dyspnea. SARS-CoV-2 is transmitted through fomites and droplets during close unprotected contact between the infected and uninfected. 1, 2, 3, 4 According to the World Health Organization’s (WHO) newly updated situation report on February 23rd 2021, the COVID-19 pandemic has reached 111,419,939 confirmed cases and claimed 2,470,772 lives, as documented globally in 223 countries worldwide ( ). The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is still spreading with devasting consequences in mortality and morbidity of human life, as well as the global economy. Finally, the specter of rapidly emerging SARS-CoV-2 variants deserves a serious review of broad-spectrum drugs or vaccines for long-term prevention and control of COVID-19 in the future. We then review the ongoing experimental studies and clinical trials of antibodies, peptides, or small-molecule compounds with anti-SARS-CoV-2 activity, and discuss how these antiviral therapies targeting host–pathogen interaction could potentially suppress viral attachment, reduce the exposure of fusion peptide to curtail membrane fusion and block the formation of six-helix bundle (6-HB) fusion core. We further explain how its spike (S) protein undergoes conformational transition from prefusion to postfusion with the help of proteases like furin, TMPRSS2, and cathepsins. In this article, we review the current knowledge and crucial information about how SARS-CoV-2 attaches on the surface of host cells through a variety of receptors, such as ACE2, neuropilin-1, AXL, and antibody–FcγR complexes. However, the underlying molecular mechanism responsible for sustaining this degree of virulence remains largely unexplored. SARS-CoV-2 has an exceptionally high level of transmissibility and extremely broad tissue tropism. The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in an unprecedented setback for global economy and health.
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