Anti-COVID-19 activity of some benzofused 1,2,3-triazolesulfonamide hybrids using in silico and in vitro analyses

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic fatal infection with no known treatment. The severity of the disease and the fast viral mutations forced the scientific community to search for potential solution. Here in the present manuscript, some benzofused1,2,3triazolesulfonamide hybrids were synthesized and evaluated for their anti- SARS-CoV-2 activity using in silico prediction then the most potent compounds were assessed using in-Vitro analysis. The in-Silico study was assessed against RNA dependent RNA polymerase, Spike protein S1, Main protease (3CLpro) and 2'-O-methyltransferase (nsp16). It was found that 4b and 4c showed high binding scores against RNA dependent RNA polymerase reached -8.40 and -8.75 Kcal/mol, respectively compared to the approved antiviral (remdesivir -6.77 Kcal/mol). Upon testing the binding score with SARS-CoV-2 Spike protein it was revealed that 4c exhibited the highest score (-7.22 Kcal/mol) compared to the reference antibacterial drug Ceftazidime (-6.36 Kcal/mol). Surprisingly, the two compounds 4b and 4c showed the highest binding scores against SARS-CoV-2 3CLpro (-8.75, -8.48 Kcal/mol, respectively) and nsp16 (- 8.84 and – 8.89 Kcal/mol, respectively) displaying many types of interaction with all the enzymes binding sites. The derivatives 4b and 4c were examined in vitro for their potential anti-SARS-CoV-2 and it was revealed that 4c was the most promising compound with IC50 reached 758.8108 mM and complete (100%) inhibition of the binding of SARS-CoV-2 virus to human ACE2 can be accomplished by using 0.01 mg.

Classifying COVID-19 based on amino acids encoding with machine learning algorithms

“…As further research directions, we aim to apply the same model using different feature extraction methods according to the sequence and the structure of the proteins to obtain more detailed biological information about the virus behavior and its infection cycle. Other classification methods will also be explored in future studies such as principal components analysis and its new derivations, including supervised and unsupervised approaches, as well as functional data analysis, partial least squares structures, and other recent methodologies [ [36] , [37] , [38] , [39] , [40] , [41] , [46] , [47] , [48] , [49] ].…”

Exploring the Antiparasitic Activity of Tris-1,3,4-Thiadiazoles against Toxoplasma gondii-Infected Mice

“…Among the four thiadiazole isomeric forms (e.g., 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, and 1,3,4-thiadiazole), the 1,3,4-thiadiazole ring is the most prevalent in medically significant synthetic compounds [ 11 , 12 , 13 ]. The 1,3,4-thidiazole nucleus is present as a core structural component in an array of drug categories, such as antifungal [ 14 ], antimicrobial [ 15 ], anti-inflammatory [ 16 ], anticancer [ 17 , 18 ], antiparasitic [ 19 ], and antiviral [ 20 ] agents. Molecular hybridization, on the other hand, is a new area in drug development that has the potential to lessen side effects and avoid drug resistance.…”

Design, Synthesis and Molecular Docking of Novel Acetophenone-1,2,3-Triazoles Containing Compounds as Potent Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors

“…Moreover, several drugs on the market, such as rufinamide (anticonvulsant), cetirizine (antibiotic), and tazobactam (antibacterial agent) have inserted a 1,2,3 triazole core into their framework [24] (Figure 1). In the literature, there are numerous 1,2,3-triazoles tethered to bioactive heterocyclic moieties, such as (Figure 2A-D), that have been documented as promising antitubercular agents [25][26][27][28][29][30][31]. In particular, the 1,4-disubstituted 1,2,3-triazole derivatives were identified and proven to have high efficacy against Mycobacterium tuberculosis.…”

“…The importance of the phenoxy methyl moiety in the development of the new candidate with significant antimycobacterium activity is represented by the lead structure (Figure 3B), which exerts its activity through inhibition of the enoyl-acyl carrier protein reductase InhA enzyme, IC50 = 0.38 µM [33]. In the literature, there are numerous 1,2,3-triazoles tethered to bioactive heterocyclic moieties, such as (Figure 2A-D), that have been documented as promising antitubercular agents [25][26][27][28][29][30][31]. In particular, the 1,4-disubstituted 1,2,3-triazole derivatives were identified and proven to have high efficacy against Mycobacterium tuberculosis.…”

“…In the literature, there are numerous 1,2,3-triazoles tethered to bioactive heterocyclic moieties, such as ( Figure 2 A–D), that have been documented as promising antitubercular agents [ 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. In particular, the 1,4-disubstituted 1,2,3-triazole derivatives were identified and proven to have high efficacy against Mycobacterium tuberculosis.…”