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

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 16; p. 5174
• Main Authors: Suručić, Relja, Radović Selgrad, Jelena, Kundaković-Vasović, Tatjana, Lazović, Biljana, Travar, Maja, Suručić, Ljiljana, Škrbić, Ranko
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 14.08.2022; MDPI
• Subjects: Alchemilla viridiflora Rothm; Antiviral drugs; Coronaviruses; COVID-19; Flavonoids; Glycoproteins; Herbal medicine; Hydrogen bonds; Infections; neuropilin-1; Pandemics; Phytochemicals; Polyphenols; Prevention; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; spike glycoprotein; Viral infections; Viruses
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27165174

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.