In Silico and In Vitro Inhibition of SARS-CoV-2 PLpro with Gramicidin D.

Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrent pandemic. Since developing a new treatment takes a significant amount of time, drug repurposing can be an effective option for achieving a rapid response. This study used a combined in silico virtual screening protocol for candidate SARS-CoV-2 PLpro inhibitors. The Drugbank database was searched first, using the Informational Spectrum Method for Small Molecules, followed by molecular docking. Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PLpro. After the expression and purification of PLpro, gramicidin D was screened for protease inhibition in vitro and was found to be active against PLpro. The current study's findings are significant because it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorable safety profile.

Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination.

BACKGROUND: Drug resistance is a critical problem in health care that affects therapy outcomes and requires new approaches to drug design. SARS-CoV-2 Mpro mutations are of concern as they can potentially reduce therapeutic efficacy. Viral infections are amongst the many disorders for which nutraceuticals have been employed as an adjunct therapy. The aim of this study was to examine the potential in vitro activity of L-arginine and vitamin C against SARS-CoV-2 Mpro. METHODS: The Mpro inhibition assay was developed by cloning, expression, purification, and characterization of Mpro. Selected compounds were then screened for protease inhibition. RESULTS: L-arginine was found to be active against SARS-CoV-2 Mpro, while a vitamin C/L-arginine combination had a synergistic antiviral action against Mpro. These findings confirm the results of our previous in silico repurposing study that showed L-arginine and vitamin C were potential Mpro inhibitors. Moreover, they suggest a possible molecular mechanism to explain the beneficial effect of arginine in COVID patients. CONCLUSIONS: The findings of the current study are important because they help to identify COVID-19 treatments that are efficient, inexpensive, and have a favorable safety profile. The results of this study also suggest a possible adjuvant nutritional strategy for COVID-19 that could be used in conjunction with pharmacological agents.

Simple Theoretical Criterion for Selection of Natural Compounds with Anti-COVID-19 Activity.

BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the leading threat to global health. An effective antiviral could not only help those still vulnerable to the virus but could be a critical treatment if a virus emerges toward evading coronavirus disease 2019 (COVID-19) vaccines. Despite the significant efforts to test already-approved drugs for their potential to kill the virus, researchers found very few actually worked. METHODS: The present report uses the electronic molecular descriptors, the quasi-valence number (AQVN), and the electron-ion interaction potential (EIIP), for the analysis of natural compounds with proven therapeutic activity against the COVID-19. RESULTS: Based on the analysis of the electronic properties of natural compounds which are effective against SARS-CoV-2 virus the simple theoretical criterion for the selection of candidate compounds for the treatment of COVID-19 is proposed. CONCLUSIONS: The proposed theoretical criterion can be used for the identification and optimization of new lead compounds for the treatment of the COVID-19 disease and for the selection of the food and food supplements which could have a beneficial effect on COVID-19 patients.

Identification of SARS-CoV-2 Papain-like Protease (PLpro) Inhibitors Using Combined Computational Approach.

In the current pandemic, finding an effective drug to prevent or treat the infection is the highest priority. A rapid and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes viral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and therefore is an attractive drug target. In this study, we used a combined in silico virtual screening for candidates for SARS-CoV-2 PLpro protease inhibitors. We used the Informational spectrum method applied for Small Molecules for searching the Drugbank database followed by molecular docking. After in silico screening of drug space, we identified 44 drugs as potential SARS-CoV-2 PLpro inhibitors that we propose for further experimental testing.

Biological Rationale for the Repurposing of BCG Vaccine against SARS-CoV-2.

The Bacillus Calmette-Guerin vaccine is still widely used in the developing world. The vaccination prevents infant death not only from tuberculosis but also from unrelated infectious agents, especially respiratory tract infections and neonatal sepsis. It is proposed that these off-target protective effects of the BCG vaccine are mediated by the general long-term boosting of innate immune mechanisms, also termed "trained innate immunity". Recent studies indicate that both COVID-19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs and encourage the initiation of several clinical studies with the expectation that revaccination with BCG could reduce the incidence and severity of COVID-19. Here, presented results from the bioinformatics analysis of the Mycobacterium bovis (strain BCG/Pasteur 1173P2) proteome suggests four immunodominant antigens that could induce an immune response against SARS-CoV-2.

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method.

The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the Informational spectrum method applied for small molecules was used for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing.