Research Article Combination Therapy of Ledipasvir and Itraconazole in the Treatment of COVID-19 Patients Coinfected with Black Fungus: An In Silico Statement Supriyo Saha , 1 Gyu Seong Yeom , 2 Satish Balasaheb Nimse , 2 and Dilipkumar Pal 3 1 School of Pharmaceutical Sciences & Technology, Sardar Bhagwan Singh University, Dehradun, 248161 Uttarakhand, India 2 Institute of Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 24252, Republic of Korea 3 Department of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), C.G, 495009, Bilaspur, India Correspondence should be addressed to Satish Balasaheb Nimse; satish_nimse@hallym.ac.kr and Dilipkumar Pal; drdilip71@gmail.com Received 26 December 2021; Revised 29 March 2022; Accepted 1 April 2022; Published 19 April 2022 Academic Editor: Mohammad Hassan Baig Copyright © 2022 Supriyo Saha et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 Rhizomucor miehei 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 Rhizomucor miehei, 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. 1. Introduction Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has threatened public health worldwide [1, 2]. It is almost a year and a half after the COVID-19 pandemic outbreak, and we are still struggling to find optimum drug therapy [3]. The emergence of the SARS-CoV-2 variants has made the situation hard to control [4, 5]. Even though the current vaccines against SARS-CoV-2 prevent severe complications and deaths effectively, the treatment options are still under validation [6, 7]. Recently, immunocompro- mised COVID-19 patients have been suffering from the coinfection of black fungus (mucormycosis) [8, 9]. COVID-19 patients with a compromised immune system or having diabetic ketoacidosis are highly prone to mucor- mycosis [10–13]. Rhizomucor, a black fungus species, causes more than 75% of cases of mucormycosis [14, 15]. Mucor- mycosis infection is directly linked with Rhizopus and Asper- gillus species (Rhizopus oryzae and Aspergillus oryzae) [16–20]. The cases of COVID-19-associated mucormycosis have been increasing worldwide since early 2021 [21], and several of such pateints have died in India [22, 23]. There- fore, drug treatment options for the combination therapy Hindawi BioMed Research International Volume 2022, Article ID 5904261, 10 pages https://doi.org/10.1155/2022/5904261