Due to the critical roles of 3CL pro and PL pro during viral polyprotein processing, both 3CL pro and PL pro have been well acknowledged as attractive antiviral drug targets. In infected cells, translation of the viral RNA initially produce 2 polyproteins, pp1a and pp1ab, which are subsequently cleaved by two viral cysteine proteases, the 3-chymotrypsin-like protease (3CL pro) and the papain-like protease (PL pro), yielding 16 mature nonstructural proteins.
SARS-CoV-2 is an enveloped, positive-stranded RNA virus, which belongs to the betacoronavirus genera. Discovery and development of more reliable with high efficacy antivirals are urgent. Regarding drug discovery and development, a repurposed drug remdesivir has been granted authorization by the Food and Drug Administration (FDA) of the United States however, the efficacy of remdesivir in the treatment of COVID-19 patients is still under debate. However, escape mutations might occur rapidly, and COVID-19 reinfection in the presence of neutralizing antibodies has been observed, these observations collectively may compromise the efficacy of vaccines. Encouraging progress has been achieved in vaccine developments, with several vaccine candidates either conditionally approved or in phase III clinical trials. Vaccines and antivirals are two major countermeasures to combat this viral infection.
The pandemic of coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to more than 93.81 million confirmed cases and approximately 2.03 million deaths globally (as of January 19, 2021, per the World Health Organization).
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