Theta-Defensins to Counter COVID-19 as Furin Inhibitors: In Silico Efficiency Prediction and Novel Compound Design

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was characterized as a pandemic by the World Health Organization (WHO) in Dec. 2019. SARS-CoV-2 binds to the cell membrane through spike proteins on its surface and infects the cell. Furin, a host-cell enzyme, possesses a binding site for the spike protein. Thus, molecules that block furin could potentially be a therapeutic solution. Defensins are antimicrobial peptides that can hypothetically inhibit furin because of their arginine-rich structure. Theta-defensins, a subclass of defensins, have attracted attention as drug candidates due to their small size, unique structure, and involvement in several defense mechanisms. Theta-defensins could be a potential treatment for COVID-19 through furin inhibition and an anti-inflammatory mechanism. Note that inflammatory events are a significant and deadly condition that could happen at the later stages of COVID-19 infection. Here, the potential of theta-defensins against SARS-CoV-2 infection was investigated through in silico approaches. Based on docking analysis results, theta-defensins can function as furin inhibitors. Additionally, a novel candidate peptide against COVID-19 with optimal properties regarding antigenicity, stability, electrostatic potential, and binding strength was proposed. Further in vitro/in vivo investigations could verify the efficiency of the designed novel peptide.

In Silico Evaluation of Nonsynonymous SNPs in Human ADAM33: The Most Common Form of Genetic Association to Asthma Susceptibility

“…Nevertheless, the probable consequences of numerous other mutations have stayed obscure. In general, genetic investigations are labor-intensive, time-consuming, and costly, while bioinformatic studies offer superior intuition into the right pathway of empirical research and considerably diminish expense and time [ 53 ]. Therefore, the present research tried to recognize functionally imperative nsSNPs in ADAM33 proteins using a variety of bioinformatic tools.…”

Host Defence Peptides: A Potent Alternative to Combat Antimicrobial Resistance in the Era of the COVID-19 Pandemic

“…Wang and co-workers reported that HD-5 can inhibit spike-protein-expressing pseudovirions from binding ACE-2 on enterocytes, ultimately preventing CoV-2 infection [166]. In silico docking studies predicted that LL-37, theta-defensins and HBD-2 can bind the RBD of SARS-CoV-2 [167][168][169]. Biochemical analyses further validated that HBD-2 indeed has strong affinity towards RBD, which prevented the fusion of S-protein expressing pseudovirions with ACE-2 on human cells [169].…”

Recent advances in antiviral effects of probiotics: potential mechanism study in prevention and treatment of SARS-CoV-2

“…Nowadays, bioinformatics tools can be used to analyze the properties of different compounds and even their biological effects with computational mathematical studies with less time and lower cost than laboratory studies and clinical trials (Negahdaripour et al 2022 ). Bioinformatics also provides accurate insight for discovering and designing creative therapeutic compounds.…”

“…There are no approved management protocols, and treatment regimens among all the drug treatments suggested to date for SARS-CoV-2 (Cunningham et al 2020 ). Numerous clinical trials were conducted to evaluate a variety of medicines such as hydroxychloroquine, lopinavir/ritonavir, corticosteroids, and remdesivir for this disease, and the clinical protocols are being updated continually (Negahdaripour et al 2022 ). The effectiveness of most of these medicines is under question for the management of SARS-CoV-2; therefore, the clinical prognosis may be unpredictable according to the lack of clinical evidence.…”