Mauritio
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This study found that vitamin K3 and certain other naphtoquinones are strong 3CL protease inhibitors. It is the main protease for coronaviruses and needed for viral replication. Thus could be highly beneficial as a treatment.
(3C-like protease - Wikipedia)
Vitamin K2 has been shown to have good binding affinity for the spike protein and has anti-viral activity as a quinone.
Unfortunately vitamin K2 did NOT work in this case, as it has a different structure.
"As thiol group of cysteine of SARS-CoV-2 3CLpro attacks the C3 position of Vitamin K3 to form the covalent bond, any bulky substitution at C3 will block the reaction. Analogues, such as Vitamin K1 and K2, have long alkyl chain substituents at C3 position, which do not form the covalent bond due to the steric hindrance."
They did however refine the molecule and looked what worked . And finally ended up with
5,8-dihydroxy-1,4-naphthoquinone, which is even more effective than K3.
"These results indicate that Vitamin K3 analogue 5,8-dihydroxy-1,4-naphthoquinone had stronger inhibitory activity and can also covalently bind to SARS-CoV-2 3CLpro as an irreversible inhibitor."
"Then we analyzed the structure-activity relationship of Vitamin K3 analogues and identified 5,8-dihydroxy-1,4-naphthoquinone with 9.8 times higher inhibitory activity than Vitamin K3."
5,8-dihydroxy-1,4-naphthoquinone,also known as Naphthazarin is an interesting compound and has anti-bacterial, anti-inflammatory and anti-tumor effects. It has also been studied as potential treatment for Parkinson's. (Error - Cookies Turned Off)
(3C-like protease - Wikipedia)
Vitamin K2 has been shown to have good binding affinity for the spike protein and has anti-viral activity as a quinone.
Unfortunately vitamin K2 did NOT work in this case, as it has a different structure.
"As thiol group of cysteine of SARS-CoV-2 3CLpro attacks the C3 position of Vitamin K3 to form the covalent bond, any bulky substitution at C3 will block the reaction. Analogues, such as Vitamin K1 and K2, have long alkyl chain substituents at C3 position, which do not form the covalent bond due to the steric hindrance."
They did however refine the molecule and looked what worked . And finally ended up with
5,8-dihydroxy-1,4-naphthoquinone, which is even more effective than K3.
"These results indicate that Vitamin K3 analogue 5,8-dihydroxy-1,4-naphthoquinone had stronger inhibitory activity and can also covalently bind to SARS-CoV-2 3CLpro as an irreversible inhibitor."
"Then we analyzed the structure-activity relationship of Vitamin K3 analogues and identified 5,8-dihydroxy-1,4-naphthoquinone with 9.8 times higher inhibitory activity than Vitamin K3."
5,8-dihydroxy-1,4-naphthoquinone,also known as Naphthazarin is an interesting compound and has anti-bacterial, anti-inflammatory and anti-tumor effects. It has also been studied as potential treatment for Parkinson's. (Error - Cookies Turned Off)
Identification of Vitamin K3 and its analogues as covalent inhibitors of SARS-CoV-2 3CLpro
After the emergence of the pandemic, repurposed drugs have been considered as a quicker way of finding potential antiviral agents. SARS-CoV-2 3CL[pro] is essential for processing the viral polyproteins into mature non-structural proteins, making it an ...
www.ncbi.nlm.nih.gov