Correction to: In silico investigation of the therapeutic and prophylactic potential of medicinal substances bearing guanidine moieties against COVID-19.

[This corrects the article DOI: 10.1007/s11696-022-02528-y.].

In silico investigation of the therapeutic and prophylactic potential of medicinal substances bearing guanidine moieties against COVID-19.

The current viral pandemic, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), creates health, mental, economic, and other serious challenges that are better to say global crisis. Despite the existence of successful vaccines, the possible mutations which can lead to the born of novel and possibly more dangerous variants of the virus as well as the absence of definitive treatment for this potentially fatal multiple-organ infection in critically ill patients make us keep searching. Theoretically targeting human and viral receptors and enzymes via molecular docking and dynamics simulations can be considered a wise, rational, and efficient way to develop therapeutic agents against COVID-19. In this way, The RNA-dependent RNA polymerase (RdRP), main protease, and spike glycoprotein of SARS-CoV-2 as well as the human angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 are the most discussed and studied targets that play essential roles in the viral life and infection cycle. In the current in silico investigation, the guanidine functionality containing drugs and medicinal substances such as metformin, famotidine, neuraminidase inhibitors, antimalarial medications, anticancer drug imatinib, CGP compounds, and human serine protease inhibitor camostat were studied against the above-mentioned therapeutic targets and most of them (especially imatinib) have revealed an incredible spectrum of free docking scores and MD results. The current in silico investigation that its novel perspective of view is corroborated by the different experimental and clinical evaluations, confirms that the guanidine moiety can be considered as a missing promising pharmacophore in drug design and development approaches against SARS-CoV-2. Considering the chemical potency of this polyamine group in chemical interaction creation, the observed outcomes in this virtual screening were not surprising. On the other hand, the guanidine functional group has unique physico-chemical properties such as basicity that can make the target cells intracellular pH undesirable for the virus entry, uncoating, and cytosolic lifecycle. According to the obtained results in the current study that are interestingly confirmed by the previously reported efficacy of some the guanidine carrying drugs in COVID-19, guanidine as a potential multi-target anti-SARS-CoV-2 functional scaffold deserves further comprehensive investigations. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02528-y.

Synthesis and In Silico Investigation of Isatin-Based Schiff Bases as Potential Inhibitors for Promising Targets against SARS-CoV-2.

Despite the significant development in vaccines and therapeutics cocktails, there is no specific treatment available for coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Targeting the main protease (Mpro) of SARS-CoV-2, which possesses a key role in producing the essential viral structural and functional proteins, can be considered an efficient way to control this potentially lethal infection. Recently, some of Michael acceptor-pharmacophore containing inhibitors have been suggested as successful suppressors of the main protease. Here, we synthesized the Isatin-based Schiff bases possessing the structural pattern of a Michael acceptor-like portion employing synthesis procedures. In silico investigation of these compounds was not limited to the main protease. We have also evaluated their possible inhibitory activity against the other identified druggable targets using homology modeling, molecular docking, and molecular dynamics simulations. Our investigations revealed that the dimethyl biguanide carrying Schiff bases of Isatin-derivatives have the best binding mode and interaction energy. The dimethyl biguanide moiety-containing compounds have formed promising interactions with the key amino acid residues Cys145 and HIS41 of Mpro with a binding free energy of -7.6 kcal/mol which was lower than the positive control compound Carmofur (-6.3 kcal/mol). It also leads to the higher affinity and the much inhibitory potential against the SARS-CoV-2 RdRp and Spike glycoproteins, human TMPRSS2, and ACE2 receptors.

Molecular docking and dynamics studies of Nicotinamide Riboside as a potential multi-target nutraceutical against SARS-CoV-2 entry, replication, and transcription: A new insight.

The highly contagious Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is a newborn infectious member of the dangerous beta-coronaviruses (ß-CoVs) following SARS and MERS-CoVs, can be regarded as the most significant issue afflicting the whole world shortly after December 2019. Considering CoVs as RNA viruses with a single-stranded RNA genome (+ssRNA), the critical viral enzyme RNA dependent RNA polymerase (RdRp) is a promising therapeutic target for the potentially fatal infection COVID-19. Nicotinamide riboside (NR), which is a naturally occurring analogue of Niacin (vitamin B3), is expected to have therapeutic effects on COVID-19 due to its super close structural similarity to the proven RdRp inhibitors. Thus, at the first phase of the current molecular docking and dynamics simulation studies, we targeted SARS-CoV-2 RdRp. On the next phase, SARS-CoV RdRp, human Angiotensin-converting enzyme 2, Inosine-5'-monophosphate dehydrogenase, and the SARS-CoV-2 Structural Glycoproteins Spike, Nonstructural viral protein 3-Chymotrypsin-like protease, and Papain-like protease were targeted using the docking simulation to find other possible antiviral effects of NR serendipitously. In the current study, the resulted scores from molecular docking and dynamics simulations as the primary determinative factor as well as the observed reliable binding modes have demonstrated that Nicotinamide Riboside and its active metabolite NMN can target human ACE2 and IMPDH, along with the viral Spro, Mpro, PLpro, and on top of all, RdRp as a potential competitive inhibitor.