The enzyme 3-chymotrypsin-like cysteine protease (3CLpro) is an important drug target in the treatment of coronavirus disease 2019 (COVID-19). Moreover, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CLpro is essential throughout the viral life cycle and exhibits high conservation among coronaviruses.
Recent studies have reported antiviral activity of flavonoids against various coronaviruses (CoV), including SARS-CoV-2.Recent microorganism A journal article describes the binding affinities and docking sites of several natural compounds and their inhibitory activity against 3CLpro.
study: Flavonoid derivatives have pancoronavirus antiviral activity. Image Credit: Kitreel / Shutterstock.com
SARS-CoV-2, a positive-stranded ribonucleic acid (RNA) virus coronavirus family Family members are the causative agents of COVID-19. Different viral enzymes such as papain-like protease (PLpro), 3CLpro, and RNA-dependent RNA polymerase (RdRp) have been used to evaluate potential anti-SARS-CoV-2 drugs.
Studies have shown a critical role for 3CLpro, also called Mpro, in antagonizing innate immunity and viral protein maturation. Compared to other human proteases, Mpro is highly conserved and is key for proteolytic processing of the viral RNA polymerase complex.
To date, mornupiravir and paxlovid are the only antiviral drugs effective in treating mild to moderate COVID-19 in patients prone to developing severe disease. Therefore, there remains an urgent need to identify new compounds that can neutralize SARS-CoV-2 and reduce its infectivity and ability to cause severe disease.
Several in silico, in vitro, When live Studies have shown that small natural molecules in the polyphenol family can interfere with coronavirus replication. Need more information about.
In the current study, molecular docking was used to filter and identify the binding affinities and docking patterns of compounds with structural similarity to flavonoids. Luteolin and 7,8-hydroxyflavone are two flavonoids that have been shown to be active against 3CLpro.
We then tested the 3CLpro inhibitory effect of compounds found to be active using several enzymatic assays. in silico. Then all active compounds are in vitro Assays to determine their anti-SARS-CoV-2 activity and potential anti-pancoronavirus activity against human (H) CoVOC43, feline (F)-CoV, and bovine (B)-CoV.
first stage of in silico Analyzes identified arnucine, baicalein, chrysin, galangin, hispidulin, isokaempferide, isosakuranetin, morin, quercetin, sakuranetin, stepogenin, and taxifolin. Using the 3CLpro enzyme assay, four flavonoids were found to be active against his 3CLpro. These included morin, baicalein, hispidulin, and isocaemphelide.
Baicalein was the most promising drug as it inhibited 3CLpro activity by >90%. Hispidulin was associated with influenza A H1N1 neuraminidase inhibition, whereas morin’s antiviral activity was observed against Herpesviridae.
The identified flavonoids are in vitro assay. Consistent with other studies, only baicalein showed greater than 50% activity against viral replication. A crystallographic image of the molecular interaction between baicalein and 3CLpro was obtained with SARS-CoV-1 3CLpro, which is very similar to SARS-CoV-2.
The researchers then evaluated the inhibitory potency of baicalein against other members of the coronavirus family. To this end, baicalein was found to be highly active against HCoV-OC43, FCoV and B-CoV replication.
Given that F-CoV belongs to the alphacoronavirus genus, baicalein may be effective against the human alpha-CoV species, which can cause severe disease in immunocompromised individuals and neonates. Baicalein’s broad antipancoronaviral effects may be caused by the fact that 3CLpro is highly conserved in cells. coronavirus family family.
A major limitation of the current study was the lack of other HCoV models to confirm baicalein’s anti-pancoronaviral activity. In addition, some compounds were tested at low concentrations as they are toxic to cells. This may have biased the assessment of the true antiviral potency of these molecules.
Together, in addition to checking in vitro Antiviral activity of baicalein against SARS-CoV-2, the current study demonstrated its anti-pancoronavirus activity.Researchers also emphasized the usefulness of combinatorial experimental approaches in silico When in vitro Analysis to identify new antiviral drugs to treat infections by SARS-CoV-2 or other viral pathogens.
These findings should prompt additional research to explore naturally occurring flavonoids and identify more 3CLpro inhibitors of SARS-CoV-2 replication. The potential activities of baicalein and its derivatives on other stages of the cycle should also be investigated.