COVID-19 is a form of severe acute respiratory syndrome caused by infection with the coronavirus SARS-CoV-2. COVID-19 emerged in China in late 2019 and rapidly became a global pandemic, prompting an enormous research effort to understand the virus and find treatments. Key areas of research include viral cell entry, viral replication and the hyperactive host immune response, known as cytokine storm. To date only one antiviral drug has been approved for treatment of COVID-19; Remdesivir, a nucleoside analogue inhibiting viral replication.
COVID-19 Disease Product Areas:
COVID-19 Research Product Areas:
SARS-CoV-2 Mechanism of Cell Entry and Replication
Figure 1: SARS-CoV-2 Viral Lifecyle. Host cell entry is effected by the binding of receptor binding domain (RBD) of the spike (S) protein on the nucleocapsid to ACE2, a protease on the host cell surface. The binding of the S protein to ACE2 is facilitated by another host cell protease, TMPRSS2 (transmembrane protease, serine 2). Following binding of S protein the virus is internalized. The internalized virus is uncoated and the SARS-CoV-2 genome is released into the cytoplasm. The viral RNA is then replicated and translated. This generates two polyproteins PP1A and PP1AB. These proteins contain within their sequence, papain-like protease (PLpro) and the coronavirus main protease (Mpro, also known as 3CLpro), which cleave the polyproteins into a variety of other functional proteins. The viral RNA also encodes the structural components of the virus, i.e. spike, nucleocapsid, membrane and envelope proteins. Following reproduction of all the viral components, coronavirus is assembled and released via vesicular exocytosis.