Promising Antiviral Activity of Agrimonia pilosa Phytochemicals against Severe Acute Respiratory Syndrome Coronavirus 2 Supported with In Vivo Mice Study

Nashwah G M Attallah; Aya H El-Kadem; Walaa A Negm; Engy Elekhnawy; Thanaa A El-Masry; Elshaymaa I Elmongy; Najla Altwaijry; Ashwag S Alanazi; Gadah Abdulaziz Al-Hamoud; Amany E Ragab

doi:10.3390/ph14121313

Promising Antiviral Activity of Agrimonia pilosa Phytochemicals against Severe Acute Respiratory Syndrome Coronavirus 2 Supported with In Vivo Mice Study

Pharmaceuticals (Basel). 2021 Dec 16;14(12):1313. doi: 10.3390/ph14121313.

Authors

Affiliations

¹ Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 84428, Saudi Arabia.
² Egyptian Drug Authority (EDA), Giza 8655, Egypt.
³ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31111, Egypt.
⁴ Pharmacognosy Department, Faculty of Pharmacy, Tanta University, Tanta 31111, Egypt.
⁵ Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Tanta 31111, Egypt.
⁶ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan 11795, Egypt.
⁷ Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.

Abstract

The global emergence of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused the entire world's attention toward searching for a potential remedy for this disease. Thus, we investigated the antiviral activity of Agrimonia pilosa ethanol extract (APEE) against SARS-CoV-2 and it exhibited a potent antiviral activity with IC₅₀ of 1.1 ± 0.03 µg/mL. Its mechanism of action was elucidated, and it exhibited a virucidal activity and an inhibition of viral adsorption. Moreover, it presented an immunomodulatory activity as it decreased the upregulation of gene expression of COX-2, iNOS, IL-6, TNF-α, and NF-κB in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells. A comprehensive analysis of the phytochemical fingerprint of APEE was conducted using LC-ESI-MS/MS technique for the first time. We detected 81 compounds and most of them belong to the flavonoid and coumarin classes. Interestingly, isoflavonoids, procyanidins, and anthocyanins were detected for the first time in A. pilosa. Moreover, the antioxidant activity was evidenced in DPPH (IC₅₀ 62.80 µg/mL) and ABTS (201.49 mg Trolox equivalents (TE)/mg) radical scavenging, FRAP (60.84 mg TE/mg), and ORAC (306.54 mg TE/g) assays. Furthermore, the protective effect of APEE was investigated in Lipopolysaccharides (LPS)-induced acute lung injury (ALI) in mice. Lung W/D ratio, serum IL-6, IL-18, IL-1β, HO-1, Caspase-1, caspase-3, TLR-4 expression, TAC, NO, MPO activity, and histopathological examination of lung tissues were assessed. APEE induced a marked downregulation in all inflammation, oxidative stress, apoptosis markers, and TLR-4 expression. In addition, it alleviated all histopathological abnormalities confirming the beneficial effects of APEE in ALI. Therefore, APEE could be a potential source for therapeutic compounds that could be investigated, in future preclinical and clinical trials, in the treatment of patients with COVID-19.

Keywords: ALI; LC-ESI-MS/MS; LPS; SARS-CoV-2; TLR-4; immunomodulatory; plaque reduction.

Grants and funding

RGP-1441-0028/the Deanship of Scientific Research (DSR), at Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia, through the Research Groups Program Grant no. (RGP-1441-0028).