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

Abstract

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 Pelargonium sidoides, 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.

From Alpha to Omicron: How Different Variants of Concern of the SARS-Coronavirus-2 Impacted the World

“…Nevertheless, to address the public health emergency of COVID-19 and the emergence of new SARS-CoV-2 variants, alternative therapies are required. Recently, the use of a broad-spectrum antiviral compound was shown to be effective in controlling viral binding and replication [ 120 ]. In a study by Subhadra et al, they used the polyphenolic-rich compound Bi121, isolated from Pelargonium sidoides, and showed potential interference in the early steps of entry and replication of the B.1.167.2 (Delta) and Omicron SARS-CoV-2, using an in vitro cell culture model [ 120 ].…”

“…Recently, the use of a broad-spectrum antiviral compound was shown to be effective in controlling viral binding and replication [ 120 ]. In a study by Subhadra et al, they used the polyphenolic-rich compound Bi121, isolated from Pelargonium sidoides, and showed potential interference in the early steps of entry and replication of the B.1.167.2 (Delta) and Omicron SARS-CoV-2, using an in vitro cell culture model [ 120 ]. Although this approach seems promising, future studies are needed to provide its efficacy in patients with COVID-19.…”

Comment on Subhadra et al. Significant Broad-Spectrum Antiviral Activity of Bi121 against Different Variants of SARS-CoV-2. Viruses 2023, 15, 1299

“…The article "Significant Broad-Spectrum Antiviral Activity of Bi121 against Different Variants of SARS-CoV-2" by Subhadra et al [1] presents a standardized polyphenolic-rich extract from Pelargonium sidoides called Bi121, with data on its antiviral activity against different SARS-CoV-2 variants and the underlying fractions of Bi121 responsible for this activity. The authors narrow down the activity to one specific compound called Neoilludin B and show RNA-intercalating activity of the compound in RNA viruses by an in silico structural modelling.…”

“…In the study of Subhadra et al [1], the Pelargonium sidoides extract Bi121 was prepared following a protocol described in literature [3], with some modifications like increased extraction temperature and the use of ultrasonication. Although described as a "standardized extract", the standardization parameter was not specified anywhere in the article.…”

“…While the extraction process for Bi121 is described to a sufficient extent, the plant material used for said extraction was not authenticated, and no voucher specimens were deposited by the authors. As a chemical fingerprint of Bi121, an HPLC chromatogram was presented (see [1], Figure 5), although no detection wavelength is specified for the chromatogram, which is crucial information. The peaks within this chromatogram are annotated by incremented numbers from 1-15 and represent "characteristic compound peaks" according to the figure caption.…”