Predicted antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir can potentially bind to neutralize SARS-CoV-2 conserved proteins

Halder, Umesh Chandra

doi:10.1186/s40709-021-00149-2

Cited by 12 publications

(4 citation statements)

References 60 publications

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“…2 . The estimated molecular docking results are also compared with previously reported work [ 42 , 43 ]. Hosseini et.…”

Section: Resultsmentioning

confidence: 89%

“…reported the binding energy for Ramelteon, Levomefolic acid, Ketoprofen etc. with main protease of SARS-CoV-2, revealing –6.0 to –6.66 kcal/mol energy score [43] . We found the binding score for the synthetic benzimidazoles against the main protease and non-structural proteins in between –5.0 to –11.0 kcal/mol, suggesting the promising inhibition actions against SARS-CoV-2.…”

Section: Resultsmentioning

confidence: 99%

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In silico anti-SARS-CoV-2 activities of five-membered heterocycle-substituted benzimidazoles

Mudi

Mahato

Verma

et al. 2022

Journal of Molecular Structure

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“…2 . The estimated molecular docking results are also compared with previously reported work [ 42 , 43 ]. Hosseini et.…”

Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

In silico anti-SARS-CoV-2 activities of five-membered heterocycle-substituted benzimidazoles

Mudi

Mahato

Verma

et al. 2022

Journal of Molecular Structure

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“…Amprenavir, a protease inhibitor approved for the therapeutic management of HIV infection by the United States Food and Drug Administration on April 15, 1999, has demonstrated e cacy with a dosing regimen of twice daily, marking a signi cant advancement over prior treatments necessitating administration every eight hours [31]. Beyond its primary application in HIV therapy, amprenavir has been explored both in vitro and in silico for potential utility in treating a range of diseases, including SARS-CoV-2 and various cancers [32,33]. Subsequent investigations have revealed that amprenavir possesses the capability to inhibit tumor cell proliferation across a diverse spectrum of cancer types, as documented [34].…”

Section: Results and Discusionmentioning

confidence: 99%

Precision Targeting Strategies in Cancer Therapy: Focusing on Synthetic Lethality with FAK Inhibition

Siyah

2024

Preprint

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Synthetic lethality, involving the simultaneous deactivation of two genes, plays a critical role in disrupting vital cellular functions or prompting cell death. This study delves into the impact of synthetic lethality within cancer research, specifically examining the interplay between the Focal Adhesion Kinase (FAK) and Neurofibromin 2 (NF2) genes. While deactivating FAK or NF2 individually has minimal impact, their combined deactivation highlights the vital significance of their synthetic lethal interaction. Hence, the principal aim of this study is to direct our efforts towards the inhibition of the FAK gene, a venture of notable significance. The NF2 gene is responsible for producing Merlin, a tumor suppressor protein that is often deactivated in schwannoma, meningioma, and malignant mesothelioma. The inhibition of the FAK gene is pivotal, given its pivotal role in the synthetic lethal interplay with NF2/Merlin, promising substantial prospects for the progression of cancer treatment strategies. This investigation has the capacity to propel forward inventive therapeutic methodologies, harnessing the potential of synthetic lethal interactions within cancer cells, and forging a path towards more refined and efficacious interventions in cancer treatment. The ongoing advancements in developing new FAK inhibitors highlight the significance of this strategy in cancer treatment. Despite extensive research efforts, no FAK inhibitor has been approved for clinical use. This emphasizes the urgent need to create new FAK inhibitors with improved anti-tumor properties. The small molecule FAK inhibitor candidates identified in our study show potential for making a groundbreaking contribution in this field. Employing docking and (1ns, 10ns and 100ns) molecular dynamics (MD) simulations, we evaluated FAK inhibitor complex stability, unveiling intricate interactions. Following of molecular dynamics simulations, the MM/GBSA scores for Amprenavir, Bosutinib, Ferric derisomaltose, Flavin adenine dinucleotide, Lactulose and Tafluprost were determined to be -72,81, -71,84, -76.70, -69.09, -74.86, -65.77 kcal/mol, respectively. These molecules have been evaluated as potential candidate drugs based on these scores. This study lays a foundation for novel therapeutics, holding promise for diverse cancer treatments through our computational framework.

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“…mol -1 ). This region of Leu235Phe substitution, located between the two domains responsible for nucleotide binding and hydrolysis, has been identified as a binding pocket for many candidate helicase inhibitors (49,50). Mutations are not only a threat to the functional roles of viral proteins, but also important for the validity of existing therapeutics.…”

Section: Discussionmentioning

confidence: 99%

The Effects of SARS CoV-2 nsp13 Mutations on the Structure and Stability of Helicase in Chinese Isolates

Akbulut¹

2022

ejb

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Objective: Coronavirus Disease 2019 (COVID19) is a viral disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2). The high mutation propensity of the SARS CoV-2 genome is one of the biggest threats to the long-term validity of treatment options. Helicases are anti-viral targets because of the vital role they play in the viral life cycle. In this study, changes in the protein structure caused by SARS CoV-2 nsp13 mutations were investigated to contribute to the development of effective antiviral drugs. Materials and Methods:Genome data of 298 individuals located in the China location were examined. The mutant model was built using deep learning algorithms. Model quality assessment was done with QMEAN. Protein stability analyses were performed with DynaMut2 and Cutoff Scanning Matrix stability. Changes in substrate affinity were performed with Haddock v2.4. Results:In this study, twenty-eight mutations in nsp13 were identified (23 sense, 5 missense). The changes in protein structure caused by the five missense mutations (Leu14Phe, Arg15Ser, Arg21Ser, Leu235Phe, Ala454Thr) were modeled. The mutations caused a decrease in the stability of SARS CoV-2 helicase (-0.99, -1.66, -1.15, -0.54, and -0.73 for Leu14Phe, Arg15Ser, Arg21Ser, Leu235Phe, Ala454Thr, respectively). The mutations reduced the helicase's affinity to the substrate. The docking scores for wild-type and mutant helicase were -84.4±1.4 kcal.mol -1 and -71.1±6.7 kcal.mol -1 , respectively. Conclusion:Helicase mutations caused a decrease in the protein stability and nucleic acid affinity of the SARS CoV-2 helicase. The results provide important data on the development of potential antivirals and the effect of mutation on the functions of viral proteins.

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Predicted antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir can potentially bind to neutralize SARS-CoV-2 conserved proteins

Cited by 12 publications

References 60 publications

In silico anti-SARS-CoV-2 activities of five-membered heterocycle-substituted benzimidazoles

In silico anti-SARS-CoV-2 activities of five-membered heterocycle-substituted benzimidazoles

Precision Targeting Strategies in Cancer Therapy: Focusing on Synthetic Lethality with FAK Inhibition

The Effects of SARS CoV-2 nsp13 Mutations on the Structure and Stability of Helicase in Chinese Isolates

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