In Search for Effective and Safe Drugs Against SARS-CoV-2: Part I] Simulated Interactions Between Selected Nutraceuticals, ACE2 Enzyme and S Protein Simple Peptide Sequences

Abstract

Coronavirus disease (COVID-19) remains a world pandemic with little treatment options. Nature has provided a plethora of compounds that may offer potential protection and/or treatment choices. Earlier studies have shown a pivotal role of Angiotensin converting enzyme 2 (ACE2) in the pathogenesis of COVID-19. In this context, seven natural compounds were selected and their binding to specific peptide sequences of the coronavirus S-protein: ACE2 interface-drug binding adduct were calculated. Further to the natural drugs, we also similarly examined four well-known antiviral drugs. Moreover, the binding-interface of the isolated coronavirus S-protein and the isolated ACE2 receptor were also individually explored. The identified drug molecules positioned itself achieving geometries of minimum energy resulting in limiting viral recognition of host cells or to disturb host-virus interactions. The frontier orbitals (HOMO-LUMO) play crucial role in the binding interactions of the studied molecules. Most of the drugs act as electron sink whereas the S protein behaves as nucleophile. The results reported pave the way for the identification of small-drug molecule of natural origin with potentially tolerable side effects that can offer protection and/or treatment against coronavirus S-protein COVID-19. Experimental validation is of urgent demand.<br>

Role of Ivermectin in Patients Hospitalized with COVID-19: A Systematic Review of Literature

“…Indeed, in-vitro models support the theory that in SARS-CoV-2 a similar inhibitory effect leading to decreased replication will be seen [14]. Computer simulations claim that ivermectin might also bind to the S protein of the virus or to ACE-2 in humans thereby warding of host cells from COVID-19 [15]. Another possible means by which ivermectin mediates its anti-viral properties is via allosteric modulation of the P2X4 receptor, which leads to the secretion of CCL-5 using ATP [16].…”