Repurposing of anti-lung cancer drugs as multi-target inhibitors of SARS-CoV-2 proteins: An insight from molecular docking and MD-simulation study

Reza, Rahimasoom; Tk, Dutta; Baildya, Nabajyoti; Ghosh, Narendra Nath; Khan, Abdul Ashik; Das, Rajesh Kumar

doi:10.1016/j.micpath.2022.105615

Cited by 8 publications

(5 citation statements)

References 63 publications

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“…It was reported that the anticancer drug Capmatinib showed the highest binding affinity, lowest Ki, and diminished toxicity values, thereby highlighting its efficacy in the dual treatment of cancer and COVID-19. [193][194][195] Hence, it can be concluded that current research is mainly focussed on anticancer agents belonging to IL inhibitors, immunomodulators, complement system inhibitors, ICI, and JAK inhibitors to name a few. However, the research is still in the trial phase and not a single agent has been approved yet due to the paucity of data and supporting patient research (Table 2).…”

Section: Covid-19 and Cancer: Manifesting Dual Treatment Module And R...mentioning

confidence: 99%

“…The challenges associated with drug repurposing are host environment differences, cellular animal assays, and sensitivity analysis, lack of powerful clinical endpoints, comorbidities, and their variability, animal models with poor predictive efficacy, lack of monitoring, and so on. [193][194][195] Walls et al recently testified the structures of the SARS-CoV-2 S-ectodomain trimer using cryo-EM to provide the required information for the design of vaccines and inhibitors against COVID-19. 211 On March 28, 2020, hydroxychloroquine (HCQ) and Remdesivir were given emergency use approval by FDA but approval of HCQ got revoked on June 15.…”

Section: Covid-19 and Cancer: Manifesting Dual Treatment Module And R...mentioning

confidence: 99%

“…Absorption, Distribution, Metabolism, Excretion, and Toxicity profiling and binding stability were assessed. It was reported that the anticancer drug Capmatinib showed the highest binding affinity, lowest Ki, and diminished toxicity values, thereby highlighting its efficacy in the dual treatment of cancer and COVID‐19 193–195 . Hence, it can be concluded that current research is mainly focussed on anticancer agents belonging to IL inhibitors, immunomodulators, complement system inhibitors, ICI, and JAK inhibitors to name a few.…”

Section: Covid‐19 and Cancer: Manifesting Dual Treatment Module And R...mentioning

confidence: 99%

“…Repurposing allows target‐based therapeutic systems to combat SARS‐CoV‐2 infection. The challenges associated with drug repurposing are host environment differences, cellular animal assays, and sensitivity analysis, lack of powerful clinical endpoints, comorbidities, and their variability, animal models with poor predictive efficacy, lack of monitoring, and so on 193–195 …”

Section: Covid‐19 and Cancer: Manifesting Dual Treatment Module And R...mentioning

confidence: 99%

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COVID‐19 and cancer: Dichotomy of the menacing dilemma

Ghosh,

Tabassum,

Basu

2023

MedComm – Oncology

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The coronavirus disease 2019 (COVID‐19) pandemic brought about unprecedented challenges to global healthcare systems. Among the most vulnerable populations are cancer patients, who face dilemmas due to their compromised immune systems and the intricate interplay with the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus. This comprehensive review delves into the multifaceted relationship between COVID‐19 and cancer. Through an analysis of existing literature and clinical data, this review unravels the structural intricacies of the virus and examines its profound implications for cancer patients, thereby bridging the knowledge gap between virology and oncology. The review commences with an introduction regarding the COVID‐19 pandemic and cancer. It then transitions into a detailed examination of the SARS‐CoV‐2 virus and its variants such as Alpha (PANGO lineage B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529 lineage). Subsequently, an insightful analysis of the impact of COVID‐19 on major cancer types (viz., Lung, Colon, Brain, and gastrointestinal cancer) is elaborated. Finally, the therapeutic avenues, oncological care, and management are discussed. The nexus between COVID‐19 and cancer adds a layer of complexity to patient care, emphasizing the importance of tailored approaches for those grappling with both conditions. Amid the landscape defined by the evolving viral strains, this review navigates through the multifaceted implications of COVID‐19 on cancer patients and underscores the significance of integrating virology and oncology.

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Section: Covid-19 and Cancer: Manifesting Dual Treatment Module And R...mentioning

confidence: 99%

Section: Covid-19 and Cancer: Manifesting Dual Treatment Module And R...mentioning

confidence: 99%

Section: Covid‐19 and Cancer: Manifesting Dual Treatment Module And R...mentioning

confidence: 99%

Section: Covid‐19 and Cancer: Manifesting Dual Treatment Module And R...mentioning

confidence: 99%

See 2 more Smart Citations

COVID‐19 and cancer: Dichotomy of the menacing dilemma

Ghosh,

Tabassum,

Basu

2023

MedComm – Oncology

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“…Lung cancer is one of the leading causes of death worldwide [ 1 ]. It has become the frequently diagnosed cancer with a high mortality rate than the other prevalent cancers (breast, colon, and pancreatic) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Potent Inhibitors Targeting EGFR and HER3 for Effective Treatment of Chemoresistance in Non-Small Cell Lung Cancer

et al. 2023

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Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Despite the existence of various therapeutic options, NSCLC is still a major health concern due to its aggressive nature and high mutation rate. Consequently, HER3 has been selected as a target protein along with EGFR because of its limited tyrosine kinase activity and ability to activate PI3/AKT pathway responsible for therapy failure. We herein used a BioSolveIT suite to identify potent inhibitors of EGFR and HER3. The schematic process involves screening of databases for constructing compound library comprising of 903 synthetic compounds (602 for EGFR and 301 for HER3) followed by pharmacophore modeling. The best docked poses of compounds with the druggable binding site of respective proteins were selected according to pharmacophore designed by SeeSAR version 12.1.0. Subsequently, preclinical analysis was performed via an online server SwissADME and potent inhibitors were selected. Compound 4k and 4m were the most potent inhibitors of EGFR while 7x effectively inhibited the binding site of HER3. The binding energies of 4k, 4m, and 7x were −7.7, −6.3 and −5.7 kcal/mol, respectively. Collectively, 4k, 4m and 7x showed favorable interactions with the most druggable binding sites of their respective proteins. Finally, in silico pre-clinical testing by SwissADME validated the non-toxic nature of compounds 4k, 4m and 7x providing a promising treatment option for chemoresistant NSCLC.

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