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Background: Thiazoles and pyridines are versatile synthetic scaffolds possessing wide spectrum of biological effects including potential antimicrobial activity. Objective: In the efforts to develop suitable antimicrobia drugs, medicinal chemists have focused on thiazole derivatives. A novel series of 2-thiazolyl pyridines was prepared in a one-pot three-component reaction using 2-bromoacetyl pyridine as a starting precursor. Method: Structure of the synthesized compounds was elucidated by spectral data (FT-IR, 1H NMR, 13C NMR, and mass) and elemental analyses. The prepared compounds were screened for their in vitro antimicrobial activity. Results: The results revealed that compounds 4a,b,e-g and 12 showed promising activity. Molecular docking studies using MOE software were carried out for compounds 4a and 4b which exhibited potent activities indicated by the diameter zones (4a; 3.6, 4.0, 1.2 mm) (4b; 4.2, 3.5, 1.5 mm) and the binding affinities (4a; -5.7731, -5.3576, -4.6844 kcal mol-1) (4b; -5.9356, -2.8250, -5.3628 kcal mol-1) against Candida albicans, Bacillus subtilis and Escherichia coli, respectively. Conclusion: This paper describes a facile and efficient MCR for synthesis of 2-thiazolyl pyridines from reaction of 2-bromoacetyl pyridine with different reagents. There was an agreement between the values of binding affinities and interactions and the data obtained from the practical antimicrobial screening of the tested compounds.

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Emergence of SARS‐CoV‐2 variants warrants sustainable efforts to upgrade both the diagnostic and therapeutic protocols. Understanding the details of cellular and molecular basis of the virus–host cell interaction is essential for developing variant‐independent therapeutic options. The internalization of SARS‐CoV‐2, into lung epithelial cells, is mediated by endocytosis, especially clathrin‐mediated endocytosis (CME). Although vaccination is the gold standard strategy against viral infection, selective inhibition of endocytic proteins, complexes, and associated adaptor proteins may present a variant‐independent therapeutic strategy. Although clathrin and/or dynamins are the most important proteins involved in CME, other endocytic mechanisms are clathrin and/or dynamin independent and rely on other proteins. Moreover, endocytosis implicates some subcellular structures, like plasma membrane, actin and lysosomes. Also, physiological conditions, such as pH and ion concentrations, represent an additional factor that mediates these events. Accordingly, endocytosis related proteins are potential targets for small molecules that inhibit endocytosis‐mediated viral entry. This review summarizes the potential of using small molecules, targeting key proteins, participating in clathrin‐dependent and ‐independent endocytosis, as variant‐independent antiviral drugs against SARS‐CoV‐2 infection. The review takes two approaches. The first outlines the potential role of endocytic inhibitors in preventing endocytosis‐mediated viral entry and its mechanism of action, whereas in the second computational analysis was implemented to investigate the selectivity of common inhibitors against endocytic proteins in SARS‐CoV‐2 endocytosis. The analysis revealed that remdesivir, methyl‐β‐cyclodextrin, rottlerin, and Bis‐T can effectively inhibit clathrin, HMG‐CoA reductase, actin, and dynamin I GTPase and are more potent in inhibiting SARS‐CoV‐2 than chloroquine. CME inhibitors for SARS‐CoV‐2 infection remain understudied.

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