Combination and tricombination therapy to destabilize the structural integrity of COVID-19 by some bioactive compounds with antiviral drugs: insights from molecular docking study

Abstract

Recently, the SARS-CoV-2 (COVID-19) pandemic virus has been spreading throughout the world. Until now, no certified drugs have been discovered to efficiently inhibit the virus. The scientists are struggling to find new safe bioactive inhibitors of this deadly virus. In this study, we aim to find antagonists that may inhibit the activity of the three major viral targets: SARS-CoV-2 3chymotrypsin-like protease (6LU7), SARS-CoV-2 spike protein (6VYB), and a host target human angiotensin-converting enzyme 2 (ACE2) receptor (1R42), which is the entry point for the viral encounter, were studied with the prospects of identifying significant drug candidate(s) against COVID-19 infection. Then, the protein stability produced score of less than 0.6 for all residues of all studied receptors. This confirmed that these receptors are extremely stable proteins, so it is very difficult to unstable the stability of these proteins through utilizing individual drugs. Hence, we studied the combination and tricombination therapy between bioactive compounds which have the best binding affinity and some antiviral drugs like chloroquine, hydroxychloroquine, azithromycin, simeprevir, baloxavir, lopinavir, and favipiravir to show the effect of combination and tricombination therapy to disrupt the stability of the three major viral targets that are mentioned previously. Also, ADMET study suggested that most of all studied bioactive compounds are safe and nontoxic compounds. All results confirmed that caulerpin can be utilized as a combination and tricombination therapy along with the studied antiviral drugs for disrupting the stability of the three major viral receptors (6LU7, 6VYB, and 1R42).

An evidence of microalgal peptides to target spike protein of COVID-19: In silico approach

“…Due to highly frequent recurrent genetic recombination SARS- CoV-2 as emerged notably in the spike glycoprotein's RBD [ 29 ]. Marine-derived compounds such as oleic acid, saringosterol, -Sitosterol, Caulerpin, Glycoglycerolipids, Kjellmanianone, and Loliolide extracted from red, green, and brown macroalgae were recently reported as candidate inhibitors against 3CL pro , the Spike protein, and the ACE-2 receptor of SARS-CoV-2 in a molecular docking-based study [ 30 ].…”

Computational Simulations Identified Marine-Derived Natural Bioactive Compounds as Replication Inhibitors of SARS-CoV-2

“…and phlorotannins isolated from marine algae Eckolina cava were able to target SARS 3CL pro through in vitro studies (De Lira et al, 2007;Park et al, 2013). A molecular docking-based study recently reported the antiviral potential of marine-derived compounds including oleic acid, saringosterol, β-Sitosterol, Caulerpin, Glycoglycerolipids, Kjellmanianone, and Loliolide isolated from red, green, and brown macroalgae as candidate inhibitors against 3CL pro , the Spike protein, and the ACE-2 receptor of SARS-CoV-2 (El-Mageed et al, 2021). Another study also reviewed the therapeutic role of Spirulina algae-derived nutraceuticals in boosting the adaptive and innate immunity against coronavirus as well as other viral diseases (Ratha et al, 2021).…”

Synthesis of the Octameric Ring Containing Compound Caulerpin Using a Knoevenagel Reaction Catalyzed by an Amino Acid ‐ Ionic Liquid Solvent

“…This hypothesis was tested by Abdelrheem's group, who evaluated the inhibition of 6LU7 using several active natural products including caulerpin [4] . Their study showed that caulerpin may be used as a potential candidate for COVID‐19 treatment, and there sare already plans of further exploring the use of Caulerpin in coronavirus triple therapy [4c] …”