Microbial diseases including viral infection are big issues globally. Effective medicinal discovery for them is the need for the day. In this study, we report pyrazole-biphenyl-carboxamides (4a-l) validated for their SARS-CoV2 entry-level restriction effect over studying the protein–protein interaction of SARS-CoV2 with human ACE protein. Their extended antimicrobial properties were also evaluated. Online and offline software tools predicted MD simulation and ADMET druggability in silico. The antimicrobial efficacy of all compounds was also evaluated against Gram+^ve Streptococcus pneumoniae (MTCC 1936), Staphylococcus aureus (MTCC 737) and Gram-^ve Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424) (bacteria). In the results, compounds 4g and 4i were evenly active against both bacteria at a low concentration range (MIC: 1.00 to 9.5 μg/mL) and displayed lesser toxicity to tested mammalian cells (EC₁₀₀ = 75 μg/mL). Furthermore, it was able to kill metabolically inactive bacterial cells and eradicate established biofilms of Methicillin-resistant Staphylococcus aureus (MRSA). Both the compounds inhibited DNA gyrase well with an IC₅₀ 0.25 μM (96% relative activity) and 0.52 μM (97% relative activity) respectively. Compounds (4a-l) showed restrictive efficiency of SARS-CoV2 spike protein (SC2SP) and human angiotensin-converting enzyme 2 (hACE2) entry-level association in COVID-19 in silico. To assess this ability, firstly, we identified the crucial amino acid residues involved in the interface of SARS-CoV-2 and hACE2 virtually. We recognized the ability of 4a-l binding to the binding interface to SARS-CoV2; thus, the interaction of SC2SP-hACE2 was effectively inhibited.

中文翻译：

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用于 SARS-CoV2 入门级限制和微生物感染的新型吡唑联苯甲酰胺

包括病毒感染在内的微生物疾病是全球性的大问题。对他们来说，有效的医学发现是当今的需要。在这项研究中，我们报告了吡唑联苯甲酰胺 ( 4a-l ) 在研究 SARS-CoV2 与人类 ACE 蛋白的蛋白质-蛋白质相互作用时验证了其 SARS-CoV2 入门级限制作用。还评估了它们的扩展抗菌特性。在线和离线软件工具通过计算机预测 MD 模拟和 ADMET 成药性。^{还评估了所有化合物对革兰氏阳性} 肺炎链球菌（MTCC 1936）、金黄色葡萄球菌（MTCC 737）和革兰氏阳性大肠杆菌（MTCC 443）、^铜绿 假单胞菌（MTCC 424）（细菌）的抗菌功效。结果显示，化合物4g和4i在低浓度范围（MIC：1.00 至 9.5 μg/mL）下对两种细菌均具有均匀的活性，并且对测试的哺乳动物细胞显示出较低的毒性（EC ₁₀₀  = 75 μg/mL）。此外，它能够杀死代谢不活跃的细菌细胞并根除已形成的耐甲氧西林金黄色葡萄球菌（MRSA）生物膜。两种化合物都能很好地抑制 DNA 旋转酶，IC ₅₀分别为 0.25 μM（96% 相对活性）和 0.52 μM（97% 相对活性）。化合物 ( 4a-l ) 在计算机模拟中显示出 SARS-CoV2 刺突蛋白 (SC2SP) 和人血管紧张素转换酶 2 ( h ACE2) 入门级关联在 COVID-19 中的限制性效率。为了评估这种能力，首先，我们虚拟地鉴定了 SARS-CoV-2 和h ACE2界面中涉及的关键氨基酸残基。我们认识到4a-l与 SARS-CoV2 结合界面结合的能力；因此，SC2SP-hACE2的相互作用被有效抑制。