More than 6.8 million people have already died as a result of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is to blame for the ongoing coronavirus disease 2019 (COVID-19) pandemic.
A recent study published in Nature Signal Transduction and Targeted Therapy showed that a novel Mpro inhibitor (SY110) may have antiviral properties against SARS-CoV-2 Omicron and its sublineages. Moreover, it was discovered to be effective against additional human coronaviruses, including Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) (MERS-CoV). SARS-CoV-2 is a member of the Coronaviridae family of the coronavirus genus. This virus has 14 open reading frames (ORFs), which code for two large polyproteins, pp1a and pp1ab, as well as four structural proteins and nine auxiliary proteins. sixteen non-structural proteins (NSPs) are produced from the polyproteins by utilizing.
A conserved gene of the virus and its variation is Mpro, also known as 3CLpro. Moreover, the Middle East respiratory syndrome coronavirus and the severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) both include this protease (MERS-CoV).
Thirteen NSPs are generated by Mpro by cleaving pp1a and pp1b. Mechanistically, Mpro specifically recognizes and cleaves amino acid sequences, with cleavage sites most frequently found at the Leu-Gln sequence. It’s significant that no human protease has the same specificity.
All things considered, Mpro may be a promising target for the creation of antivirals. Remdesivir, Molnupiravir, and Paxlovid are only a few of the small compounds that have received approval as antiviral medications. Simnotrelvir, Ensitrelvir, and Nirmatrelvir are SARS-CoV-2 Mpro inhibitors. Yet these antivirals have some toxicity problems, poor potency, and poor pharmacokinetics (PK) properties, such as poor oral bioavailability, poor oral bioavailability, and modest stability in human liver microsomes (HLM).
