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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 spread rapidly around the globe. Common disease symptoms are cough, fever, shortness of breath, fatigue and loss of sense of taste and smell, which are generally mild. However, in some patients, particularly the elderly or those with other pre-existing conditions such as diabetes or cardiovascular disease, the disease may progress to acute respiratory distress syndrome (ARDS), multiple organ failure, sepsis and death.
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.
Since the emergence of COVID-19, a great deal of research has been carried out to determine the structure of the virus and the mechanisms by which it infects cells and replicates in order to discover points in the lifecycle with potential as prophylactic or therapeutic targets. SARS-CoV-2 is an enveloped positive-sense single-stranded RNA virus contained in a nucleocapsid. Potential targets for intervention include viral entry into the host cell, which is enabled by the binding of the Spike protein on the surface of the virus to ACE2, a host cell membrane protease. ACE2 is expressed on epithelial and endothelial cells particularly in the lungs and gastrointestinal tract. Viral proteases associated with viral replication, such as Mpro and PLpro, are also potential targets.
A wide range of approved medicines, including antivirals and antimalarials, have been investigated for their ability to interact with these targets, with the aim of repurposing them as therapies for COVID-19.
Multiple drugs that are used to treat other disorders have been identified as potential treatments for COVID-19. This blog post outlines the SARS-CoV-2 mechanism of cell entry and highlights the targets of drugs that are under investigation for repurposing in COVID-19 treatment.Read Now!
Tocris offers the following scientific literature for COVID-19 Research to showcase our products. We invite you to request* or download your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.