Coronaviruses (CoVs; subfamily Coronavirinae, family Coronaviridae, order Nidovirales) are enveloped, positive-sense single-stranded RNA viruses. CoVs can be classified into four genera: Alphacoronavirus, Betacoronavirus (βCoV), Gammacoronavirus and Deltacoronavirus. CoVs are zoonotic pathogens that can cause respiratory, enteric, hepatic and neurological diseases in birds and mammals including humans. CoVs primarily target epithelial cells and are generally associated with gastrointestinal and respiratory infections. In general, these infections are mild and often asymptomatic. However CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), can cause severe and even lethal disease with prolonged shedding of virus.
The SARS-CoV2 is a novel coronavirus identified as the cause of the coronavirus disease 2019 (COVID-19) pandemic that began in Wuhan, China in 2019. SARS-CoV-2 can cause severe diseases such as pneumonia, acute respiratory distress syndrome (ARDS), sepsis, septic shock or multiple organ failure, particularly among the elderly and immunocompromised patients. Phylogenetical analysis revealed that SARS-CoV-2 is a βCoV. The genome sequence of SARS-CoV-2 is 96.2% identical to a bat CoV RaTG13 and 79.5% identity to SARS-CoV. Bats are suspected to be the natural reservoir species for the progenitor virus and SARS-CoV-2 may have been transmitted from bats via an intermediate hosts to infect humans. SARS-CoV-2 virus particle are has round, elliptic and often pleomorphic in shape and a diameter of approximately 60–140 nm. The SARS-CoV2 genome encodes four essential structural proteins including the spike (S) glycoprotein, nucleocapsid (N) protein, membrane (M) protein, and the envelope (E) protein, , and also several accessory proteins
CoVs enter the host cell via the endosomal pathway and/or the cell surface non-endosomal pathway and release their genome into the target cell. The S glycoprotein facilitates viral entry into host target cell by directly binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor. ACE2 is a zinc metalloenzyme and carboxypeptidase which is highly expressed lungs, kidney, endothelium and heart. The S glycoprotein is activated and cleaved by host proteases, such as transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, which enables cell surface non-endosomal virus entry at the plasma membrane. CoVs then release the viral genome RNA into the cytoplasm and the uncoated RNA translates two polyproteins, pp1a and pp1ab. Extensive autoproteolytic processing of pp1a and pp1ab by main protease (MPro) and 3C-like protease (3CLpro) produce mature non-structural proteins (NSPs), RNA-dependent RNA polymerase (RdRp) and helicase essential for replication. RdRp, NSps and host factors assemble into membrane-bound replication-transcription complexes (RTC) to synthesize viral RNA. Newly formed genomic RNA, nucleocapsid proteins and envelope glycoproteins assemble and form viral particle buds that fuse with the plasma membrane to release the virus.