In Silico and In Vitro Studies of Alchemilla viridiflora Rothm—Polyphenols’ Potential for Inhibition of SARS-CoV-2 Internalization

Abstract

Since the outbreak of the COVID-19 pandemic, it has been obvious that virus infection poses a serious threat to human health on a global scale. Certain plants, particularly those rich in polyphenols, have been found to be effective antiviral agents. The effectiveness of Alchemilla viridiflora Rothm. (Rosaceae) methanol extract to prevent contact between virus spike (S)-glycoprotein and angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors was investigated. In vitro results revealed that the tested samples inhibited 50% of virus-receptor binding interactions in doses of 0.18 and 0.22 mg/mL for NRP1 and ACE2, respectively. Molecular docking studies revealed that the compounds from A. viridiflora ellagitannins class had a higher affinity for binding with S-glycoprotein whilst flavonoid compounds more significantly interacted with the NRP1 receptor. Quercetin 3-(6”-ferulylglucoside) and pentagalloylglucose were two compounds with the highest exhibited interfering potential for selected target receptors, with binding energies of −8.035 (S-glycoprotein) and −7.685 kcal/mol (NRP1), respectively. Furthermore, computational studies on other SARS-CoV-2 strains resulting from mutations in the original wild strain (V483A, N501Y-K417N-E484K, N501Y, N439K, L452R-T478K, K417N, G476S, F456L, E484K) revealed that virus internalization activity was maintained, but with different single compound contributions.

Natural products as a source of Coronavirus entry inhibitors

“…Broadly speaking, flavonoids such as myricetin are some of the most promising natural drug candidates for antiviral development. Multiple studies have demonstrated the S-ACE2 inhibitory activity of compounds such as epicatechin, luteolin, curcumin, and quercetin using a variety of in vitro and in silico methodologies ( Goc et al., 2021b ; Zhan et al., 2021 ; Al-Shuhaib et al., 2022 ; Chen C. et al., 2022 ; Nag et al., 2022 ; Ohishi et al., 2022 ; Suručić et al., 2022 ; Gao et al., 2023 ; Zhu et al., 2023 ). Other polyphenolic compounds display similar potential, including ellagitannins and carboxylic acids which have some of the most potent S-ACE2 IC 50 values in recent literature, often in the nanomolar range ( Table 3 ) ( Mei et al., 2021 ; Invernizzi et al., 2022 ).…”