Nat Commun: COVID-19 Treatment New hope, cat coronavirus treatment drugs, can effectively inhibit the replication of the new coronavirus!

As of September 1, new crown pneumonia (COVID-19) caused by SARS-CoV-2 has infected more than 25 million people worldwide and killed more than 850,000.
the need to develop long-acting vaccines and antiviral drugs for COVID-19 infections.
In earlier studies, scientists found that the main protease (Mpro, also known as 3CLpro) in SARS-CoV-2 was an important potential drug target, capable of cutting the polyproteins translated into the human body after viral RNA entered the body into smaller proteins, essential to inhibit virus replication.
Recently, a team of researchers from the University of Alberta in Canada found that the protease inhibitor GC376 and its mother GC373, which had been used earlier to treat cat coronavirus infection, effectively inhibited Mpro of SARS-CoV and SARS-CoV-2 in the Namore range, by reversible formation of semi-sulfur adehyde.
addition, these two compounds can effectively inhibit the replication of SARS CoV-2 in cell culture and are strong candidates for the treatment of human coronavirus infection.
results were published in Nature Communications on August 27, local time.
As early as 2003, the team developed GC376, an inhibitor of the viral cysteine protease, which is used to suppress FCoV10, the cat coronavirus that causes cat-borne perititis (FIP).
Since Mpro in SARS-CoV-2 is also a cysteine protease, the researchers first tested GC376 and its parent GC373 with IC50 for effective inhibition of SARS-CoV-2 Mpro and SARS-CoV Mpro (the coronavirus that causes SARS, which has a high sygenesity with the new coronavirus), and found that both viruses Compounds have a wide range of inhibitory effects, both in-body inhibition of SARS-CoV-2 Mpro and SARS-CoV Mpro at namore concentrations, and GC376 is more effective than GC373, and its binding to SARS-CoV-2 Mpro is closer to known Mpro inhibitors in other tests such as eb selenium and ketoamide inhibitors.
Mpro of GC373 and GC376 in-body inhibition of SARS-CoV-2 and SARS-CoV To learn more about their inhibition, the researchers measured the crystal structure of GC373 and GC376 inhibition of SARS-CoV-2 Mpro and found that in both In the structure, inhibitors are co-priced in the form of semi-sulfur adehyde connected to SARS-CoV-2 Mpro Cys145, through the hydrophobic interaction between the compound and protease and hydrogen bond network to stabilize the inhibitor at the active point of protease, which also provides inhibitors with a stronger binding force and lower IC50.
addition to the crystal structure of SARS-CoV-2 Mpro composited with GC373 (converted by GC376), crystal structure analysis found that the residuals of SARS-CoV-2 Mpro diamer interface differ from SARS-CoV Mpro, while previous studies have shown that the residuals of SARS-CoV Mpro diamer interfaces (especially T285A, i.e. 28) are altered. The catalytic activity of five amino acids from T mutation A increases its catalytic activity by 3.6 times, which happens to be 285 times that of SARS-CoV-2 Mpro is alanine A, so the researchers tested the catalytic activity of these two proteases through a substrate catalytic test and found that the catalytic conversion rate of SARS-CoV-2 Mpro was five times higher than that of SARS-CoV Mpro.
also indicates that SARS-CoV-2 Mpro has stronger catalytic activity than SARS-CoV Mpro.
, the researchers conducted a plaque reduction test on infected Vero E6 cells to test GC373 and GC376 for inhibition of SARSCoV-2 and to test their antiviral activity through virus yield reduction analysis.
results showed that both GC373 and GC376 were able to effectively suppress SARS-CoV-2, GC373 EC50 was 1.5 m, and GC376 EC50 was 0.92 m, which was better than other known inhibitors tested so far.
also shows that GC373 and GC376 are both effective inhibitors of SARS-CoV-2, and that the therapeutic index (TI) is greater than 200, which is safer.
GC373 and GC376 were effective in suppressing SARS-CoV-2 In short, the study found that GC373 and GC376, two drugs used to treat coronavirus infections in cats, were effective in suppressing the main proteases in SARS-CoV-2, as well as the ability to inhibit INtracellular SARS-CoV-2, a potential treatment for pneumonia.
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