Investigating the promising SARS-CoV-2 main protease inhibitory activity of secoiridoids isolated from Jasminum humile; in silico and in Vitro assessments with structure-activity relationship

Ahmed A Al-Karmalawy; Radwan Alnajjar; Ayman Abo Elmaaty; Faizah A Binjubair; Sara T Al-Rashood; Basma S Mansour; Ahmed Elkamhawy; Wagdy M Eldehna; Khaled Ahmed Mansour

doi:10.1080/07391102.2023.2240419

Investigating the promising SARS-CoV-2 main protease inhibitory activity of secoiridoids isolated from Jasminum humile; in silico and in Vitro assessments with structure-activity relationship

J Biomol Struct Dyn. 2023 Jul 28:1-13. doi: 10.1080/07391102.2023.2240419. Online ahead of print.

Authors

Ahmed A Al-Karmalawy¹, Radwan Alnajjar^{2

3}, Ayman Abo Elmaaty⁴, Faizah A Binjubair⁵, Sara T Al-Rashood⁵, Basma S Mansour⁵, Ahmed Elkamhawy^{6

7}, Wagdy M Eldehna^{8

9}, Khaled Ahmed Mansour¹⁰

Affiliations

¹ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt.
² Department of Chemistry, Faculty of Science, University of Benghazi, Benghazi, Libya.
³ PharmD, Faculty of Pharmacy, Libyan International Medical University, Benghazi, Libya.
⁴ Department of Medicinal Chemistry, Faculty of Pharmacy, Port Said University, Port Said, Egypt.
⁵ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁶ BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea.
⁷ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
⁸ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt.
⁹ School of Biotechnology, Badr University in Cairo, Badr City, Egypt.
¹⁰ Department of Pharmacognosy, Faculty of Pharmacy, Horus University in Egypt, New Damietta, Egypt.

PMID: 37505066
DOI: 10.1080/07391102.2023.2240419

Abstract

The proteolytic enzyme 3 C-like protease (3Clpro or M^pro) is considered the most important target for SARS-CoV-2 which could be attributed to its crucial role in viral maturation and/or replication. Besides, natural phytoconstituents from plant origin are always promising lead compounds in the drug discovery area. Herein, the previously isolated and identified seven compounds from Jasminum humile (J. humile) were examined in vitro and in silico against the SARS-CoV-2 M^pro. First, the Vero E6 cells were utilized to pursue the potential of the investigated compounds (both in fractions and individual isolates) using the MTT assay. The total extract (T1) displayed the most significant activity against SARS-CoV-2 with IC₅₀ = 29.36 µg/mL. Besides, the fractions (Fr1 and Fr3) showed good activity against the SARS-CoV-2 with IC₅₀ values of 70.42, and 73.09 µg/mL, respectively. Then, the SARS-CoV-2 M^pro inhibitory assay was utilized to emphasize the inhibitory potential of the investigated isolates. MJN, JMD, and IJM candidates displayed prominent M^pro inhibitory potentials with IC₅₀ = 30.44, 30.24, and 56.25 µM, respectively. Moreover, molecular docking of the identified seven compounds against the M^pro of SARS-CoV-2 showed that the five secoiridoids achieved superior results. MJN, JSM, IJM, and JMD showed higher affinities towards the M^pro target compared to the co-crystallized antagonist. Furthermore, the most active complexes (MJN, JSM, IJM, and JMD-M^pro) were subjected to MD simulations run for 150 ns and MM-GBSA calculations, compared to the co-crystallized inhibitor (O6K-M^pro). Finally, the SAR study clarified that JMD achieved the best anti-SARS-CoV-2 M^pro activity followed by MJN.Communicated by Ramaswamy H. Sarma.

Keywords: COVID-19; Jasminum humile; SAR; anti-SARS-CoV-2; mpro inhibitory assay.

Plain language summary

HIGHLIGHTSSeven isolates from J. humile, besides different extracts, were examined both in vitro and in silico.Anti-SARS-CoV-2 using the MTT assay and anti-SARS-CoV-2 Mpro inhibitory assay were performed.Compounds MJN, JMD, and IJM displayed prominent SARS-CoV-2 Mpro inhibition.Molecular docking, molecular dynamics simulations, and MM-GBSA calculations were carried out.SAR study was conducted on the isolated compounds.