School of Pharmaceutical Sciences & Technology, Sardar Bhagwan Singh University, Dehradun, 248161 Uttarakhand, India.
Institute of Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 24252, Republic of Korea.
Biomed Res Int. 2022 Apr 19;2022:5904261. doi: 10.1155/2022/5904261. eCollection 2022.
The manuscript mainly aimed at providing clues on improving the innate immunity of coronavirus patients and safeguarding them from both new mutant strains and black fungus infections. Coronavirus is readily mutating from one variant to another. Among the several variants, we selected SARS-CoV-2 B.1.1.7 in this study. Upon infection of any virus, ideally, the phagocytic cells of the host engulf and destroy the virus by a mechanism called phagocytosis. However, compromised immunity impairs phagocytosis, and thus, restoring the immune system is crucial for a speedy recovery of infected patients. The autophagy and activation of Toll-like receptor-4 are the only ways to restore innate immunity. Recently, immunocompromised COVID-19 patients have been suffering from the coinfection of black fungus. Rhizomucor, a black fungus species, causes more than 75% of cases of mucormycosis. Here, we present the results of molecular docking studies of sixty approved antiviral drugs targeting receptors associated with the SARS-CoV-2 B 1.1.7 variant (PDB id: 7NEH), activating the innate immune system (PDB id: 5YEC and 5IJC). We also studied the twenty approved antifungal drugs with lipase propeptide (PDB id: 6QPR) to identify the possible combination therapy for patients coinfected with coronavirus and black fungus. The ledipasvir showed excellent docking interactions with the 7NEH, 5YEC, and 5IJC, indicating that it is a perfect candidate for the treatment of COVID-19 patients. Itraconazole showed significant interaction with 6QPR of , suggesting that itraconazole can treat black fungus infections. In conclusion, the combination therapy of ledipasvir and itraconazole can be a better alternative for treating COVID-19 patients coinfected with black fungus.
本文主要旨在为提高冠状病毒患者的固有免疫力提供线索，使他们免受新的变异株和黑霉菌感染。冠状病毒很容易从一种变体突变到另一种变体。在几种变体中，我们在这项研究中选择了 SARS-CoV-2 B.1.1.7。当任何病毒感染时，理想情况下，宿主的吞噬细胞通过吞噬作用机制吞噬并破坏病毒。然而，免疫功能受损会削弱吞噬作用，因此，恢复免疫系统对于感染患者的快速康复至关重要。自噬和 Toll 样受体 4 的激活是恢复固有免疫的唯一途径。最近，免疫功能低下的 COVID-19 患者一直遭受黑霉菌的合并感染。毛霉，一种黑霉菌，引起超过 75%的毛霉菌病病例。在这里，我们介绍了针对与 SARS-CoV-2 B 1.1.7 变体相关的受体的六十种已批准抗病毒药物（PDB id：7NEH）和激活固有免疫系统（PDB id：5YEC 和 5IJC）的分子对接研究结果。我们还研究了与脂酶前肽（PDB id：6QPR）结合的二十种已批准抗真菌药物，以确定冠状病毒和黑霉菌合并感染患者的可能联合治疗方案。利迪帕韦与 7NEH、5YEC 和 5IJC 显示出优异的对接相互作用，表明它是治疗 COVID-19 患者的理想候选药物。伊曲康唑与 6QPR 的 显示出显著的相互作用，表明伊曲康唑可以治疗黑霉菌感染。总之，利迪帕韦和伊曲康唑的联合治疗可能是治疗冠状病毒和黑霉菌合并感染患者的更好选择。
