Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An in Silco Study for Drug Development

Preeti Pandey, Jitendra Subhash Rane, Aroni Chatterjee, Abhijeet Kumar, Rajni Khan, Amresh Prakash, Shashikant Ray

10.1080/07391102.2020.1796811

Research curated

Abstract

Spike glycoprotein, a class I fusion protein harboring the surface of SARS-CoV-2 (SARS-CoV-2S), plays a seminal role in the viral infection starting from recognition of the host cell surface receptor, attachment to the fusion of the viral envelope with the host cells. Spike glycoprotein engages host Angiotensin-converting enzyme 2 (ACE2) receptors for entry into host cells, where the receptor recognition and attachment of spike glycoprotein to the ACE2 receptors is a prerequisite step and key determinant of the host cell and tissue tropism. Binding of spike glycoprotein to the ACE2 receptor triggers a cascade of structural transitions, including transition from a metastable pre-fusion to a post-fusion form, thereby allowing membrane fusion and internalization of the virus. From ancient times people have relied on naturally occurring substances like phytochemicals to fight against diseases and infection. Among these phytochemicals, flavonoids and non-flavonoids have been the active sources of different anti-microbial agents. We performed molecular docking studies using 10 potential naturally occurring compounds (flavonoids/non-flavonoids) against the SARS-CoV-2 spike protein and compared their affinity with an FDA approved repurposed drug hydroxychloroquine (HCQ). Further, our molecular dynamics (MD) simulation and energy landscape studies with fisetin, quercetin, and kamferol revealed that these molecules bind with the hACE2-S complex with low binding free energy. The study provided an indication that these molecules might have the potential to perturb the binding of hACE2-S complex. In addition, ADME analysis also suggested that these molecules consist of drug-likeness property, which may be further explored as anti-SARS-CoV-2 agents.

Source: PubMed

Related molecules

Name	Synonyms	Genes
pterostilbene
Fisetin
isorhamnetin
genistein
apigenin
resveratrol
Kaempferol	Kamferol
Quercetin
luteolin	Luteolol, Digitoflavone, Flacitran, Luteoline
Spike glycoprotein	Spike protein, S glycoprotein, S-Protein, S1, S2, S3, Peplomer protein, E2	S, ORF2
Curcumin
Hydroxychloroquine	HCQ, Oxichlorochine, Oxichloroquine

Related interactions

Target	Drug	Type	Result
Spike glycoprotein	Kaempferol	Computational	positive
Spike glycoprotein	pterostilbene	Computational	positive
Spike glycoprotein	Fisetin	Computational	positive
Spike glycoprotein	Quercetin	Computational	positive
Spike glycoprotein	isorhamnetin	Computational	positive
Spike glycoprotein	genistein	Computational	positive
Spike glycoprotein	luteolin	Computational	positive
Spike glycoprotein	resveratrol	Computational	positive
Spike glycoprotein	apigenin	Computational	positive
Spike glycoprotein	Hydroxychloroquine	Computational	positive
Spike glycoprotein	Curcumin	Computational	positive