How do arbidol and its analogs inhibit the SARS-CoV-2?

Area of Science:

• Virology
• Computational Chemistry
• Drug Discovery

Background:

• COVID-19, a global health crisis, causes severe inflammation and cytokine storms, with symptoms including fever, dyspnea, and diarrhea.
• Arbidol, a hemagglutinin esterase inhibitor, has been used in COVID-19 treatment, but its efficacy remains questionable.
• Despite limited success, Arbidol continues to be used in various countries for COVID-19 management.

Purpose of the Study:

• To investigate the in silico efficacy of Arbidol, a hemagglutinin esterase inhibitor, against SARS-CoV-2.
• To evaluate Arbidol and its analogues' inhibitory properties against hemagglutinin esterase and spike glycoproteins.

Main Methods:

• In silico analysis of Arbidol and 39 analogues against hemagglutinin esterase and SARS-CoV-2 spike glycoproteins.
• Examination of the interaction mechanisms between Arbidol and spike protein binding domains.

Main Results:

• Arbidol analogues CID 1070884 and CID 1207786 demonstrated greater activity against hemagglutinin esterase compared to Arbidol.
• These specific analogues were found to be inactive against SARS-CoV-2 spike glycoproteins.
• The study elucidated the interaction mechanism between Arbidol and the binding domains of SARS-CoV-2 spike glycoproteins.

Conclusions:

• Arbidol's in silico activity against SARS-CoV-2 spike proteins is limited, suggesting it may not be an effective therapeutic agent.
• Specific amino acids, including phenylalanine, tyrosine, glycine, lysine, and aspartic acid, are crucial for Arbidol's interaction with spike glycoproteins.
• Further research into Arbidol analogues may yield more effective inhibitors, but current evidence does not support its use against SARS-CoV-2 spike proteins.