Golchha Nikita Chordia, Abdulhameed Odhar Hasanain, Nighojkar Anand, Nighojkar Sadhana
School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, INDORE-452001, India.
Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq.
Bioinformation. 2024 Jan 31;20(1):39-48. doi: 10.6026/973206300200039. eCollection 2024.
The opportunistic pathogen, owes its extreme pathogenicity for its ability to develop antibiotic resistance and recurrent infections. The current antibiotics used for the treatment are showing declining sensitivity and rising antibiotic resistance. Therefore, it is of interest to develop the anti-clostridial drugs to overcome these issues. Hence, we have explored ZINC library to find the suitable lead compounds against five target proteins of . Multistep virtual screening is performed to find the suitable compounds that are checked for their stability using molecular dynamics and are validated against . In our study, five compounds viz., ZINC64969876, ZINC13641164, ZINC13691348, ZINC5554596 and ZINC3894278 that inhibit HisC, Spo0A, PdcA, DAHP synthase and cyclic-di GMP proteins, respectively have been identified. Further, these compounds were tested against four different isolates of and all of them were found to inhibit the pathogen. However, to use these compounds as anti-clostridial drugs, further testing needs to be done. The selected compounds from our study are reported for the first time as antimicrobial agents against .
这种机会致病菌因其产生抗生素耐药性和反复感染的能力而具有极强的致病性。目前用于治疗的抗生素敏感性在下降，抗生素耐药性在上升。因此，开发抗梭菌药物以解决这些问题具有重要意义。为此，我们探索了ZINC文库，以寻找针对[具体细菌名称]五种靶蛋白的合适先导化合物。进行了多步虚拟筛选，以找到合适的化合物，使用分子动力学检查其稳定性，并针对[具体参照标准]进行验证。在我们的研究中，已鉴定出五种分别抑制HisC、Spo0A、PdcA、DAHP合酶和环二鸟苷酸蛋白的化合物，即ZINC64969876、ZINC13641164、ZINC13691348、ZINC5554596和ZINC3894278。此外，这些化合物针对[具体细菌名称]的四种不同分离株进行了测试，发现它们均能抑制该病原体。然而，要将这些化合物用作抗梭菌药物，还需要进一步测试。我们研究中所选的化合物作为针对[具体细菌名称]的抗菌剂首次被报道。
