Significant Broad-Spectrum Antiviral Activity of Bi121 against Different Variants of SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has so far infected 762 million people with over 6.9 million deaths worldwide. Broad-spectrum viral inhibitors that block the initial stages of infection by reducing virus binding and proliferation, thereby reducing disease severities, are...

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Bibliographic Details
Published in:Viruses 2023-05, Vol.15 (6), p.1299
Main Authors: Subhadra, Bobban, Agrawal, Ragini, Pal, Virender Kumar, Chenine, Agnes-Laurence, Mattathil, Jeffy George, Singh, Amit
Format: Article
Language:English
Subjects:
ACE2
Angiotensin-converting enzyme 2
Animals
antiviral
Antiviral activity
Antiviral agents
Antiviral Agents - pharmacology
Bi121
Cell lines
Chlorocebus aethiops
Clinical trials
Coronaviruses
COVID-19
COVID-19 vaccines
Dosage and administration
Drug resistance
Fractionation
Hospitalization
Humans
Medical research
Medicine, Experimental
Mutation
Neoilludin B
Pelargonium sidoides
Peptides
Polyphenols
Proteins
Respiratory diseases
RNA polymerase
RNA viruses
SARS-CoV-2
SARS-CoV-2 - genetics
Severe acute respiratory syndrome coronavirus 2
Solvents
Spike Glycoprotein, Coronavirus - genetics
Spike protein
Stomatitis
Tandem Mass Spectrometry
Vero Cells
Vesiculovirus
Viruses
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Summary:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has so far infected 762 million people with over 6.9 million deaths worldwide. Broad-spectrum viral inhibitors that block the initial stages of infection by reducing virus binding and proliferation, thereby reducing disease severities, are still an unmet global medical need. We studied Bi121, which is a standardized polyphenolic-rich compound isolated from , against recombinant vesicular stomatitis virus (rVSV)-pseudotyped SARS-CoV-2S (mutations in the spike protein) of six different variants of SARS-CoV-2. Bi121 was effective at neutralizing all six rVSV-ΔG-SARS-CoV-2S variants. The antiviral activity of Bi121 was also assessed against SARS-CoV-2 variants (USA WA1/2020, Hongkong/VM20001061/2020, B.1.167.2 (Delta), and Omicron) in Vero cells and HEK-ACE2 cell lines using RT-qPCR and plaque assays. Bi121 showed significant antiviral activity against all the four SARS-CoV-2 variants tested, suggesting a broad-spectrum activity. Bi121 fractions generated using HPLC showed antiviral activity in three fractions out of eight against SARS-CoV-2. The dominant compound identified in all three fractions using LC/MS/MS analysis was Neoilludin B. In silico structural modeling studies with Neoilludin B showed that it has a novel RNA-intercalating activity toward RNA viruses. In silico findings and the antiviral activity of this compound against several SARS-CoV-2 variants support further evaluation as a potential treatment of COVID-19.
ISSN:1999-4915
1999-4915
DOI:10.3390/v15061299