Computational and <i>in vitro</i> experimental analyses of the anti-COVID-19 potential of Mortaparib and MortaparibPlus

Kumar, Vipul; Sari, Anissa Nofita; Meidinna, Hazna Noor; Dhanjal, Jaspreet Kaur; Subramani, Chandru; Basu, Brohmomoy; Kaul, Sunil C.; Vrati, Sudhanshu; Sundar, Durai; Wadhwa, Renu

doi:10.1042/bsr20212156

Cited by 4 publications

(2 citation statements)

References 46 publications

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“…Finally, drug prediction that targets key genes is feasible. For example, the inhibitor developed for the polymerase PARP-1 and HSPA9 can be used against COVID-19 [ 38 ]. We performed drug predictions using cMAP for the 81 common DEGs.…”

Section: Discussionmentioning

confidence: 99%

Exploring Potential Biomarkers and Molecular Mechanisms of Ischemic Cardiomyopathy and COVID-19 Comorbidity Based on Bioinformatics and Systems Biology

Luo

Zhang

et al. 2023

IJMS

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Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and COVID-19 is still unclear. Here, we explored potential molecular mechanisms and biomarkers for ICM and COVID-19. Common differentially expressed genes (DEGs) of ICM (GSE5406) and COVID-19 (GSE164805) were identified using GEO2R. We performed enrichment and protein–protein interaction analyses and screened key genes. To confirm the diagnostic performance for these hub genes, we used external datasets (GSE116250 and GSE211979) and plotted ROC curves. Transcription factor and microRNA regulatory networks were constructed for the validated hub genes. Finally, drug prediction and molecular docking validation were performed using cMAP. We identified 81 common DEGs, many of which were enriched in terms of their relation to angiogenesis. Three DEGs were identified as key hub genes (HSP90AA1, HSPA9, and SRSF1) in the protein–protein interaction analysis. These hub genes had high diagnostic performance in the four datasets (AUC > 0.7). Mir-16-5p and KLF9 transcription factor co-regulated these hub genes. The drugs vindesine and ON-01910 showed good binding performance to the hub genes. We identified HSP90AA1, HSPA9, and SRSF1 as markers for the co-pathogenesis of ICM and COVID-19, and showed that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis. Vindesine and ON-01910 were predicted as potential therapeutic agents. Our findings will contribute to a deeper understanding of the comorbidity of ICM with COVID-19.

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Section: Discussionmentioning

confidence: 99%

Exploring Potential Biomarkers and Molecular Mechanisms of Ischemic Cardiomyopathy and COVID-19 Comorbidity Based on Bioinformatics and Systems Biology

Luo

Zhang

et al. 2023

IJMS

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“…SARS-CoV-2 is composed of capsids and nucleocapsids. The capsid is mainly composed of three structural proteins: spike (S) protein, envelope (E) protein, and matrix (M) protein . It is primarily responsible for the binding and fusion of the virus into the host membrane, ion exchange between the virus and the external environment, and virus assembly and budding. , The nucleocapsid consists of nucleocapsid (N) protein and the viral genomic RNA.…”

Section: Introductionmentioning

confidence: 99%

New Strategies for Responding to SARS-CoV-2: The Present and Future of Dual-Target Drugs

Zhang,

Xiao,

et al. 2024

J. Med. Chem.

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The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of deaths, posing a serious threat to public health and safety. Rapid mutations of SARS-CoV-2 and complex interactions among multiple targets during infection pose a risk of expiry for small molecule inhibitors. This suggests that the traditional concept of "one bug, one drug" could be ineffective in dealing with the coronavirus. The dual-target drug strategy is expected to be the key to ending coronavirus infections. However, the lack of design method and improper combination of dual-targets poses obstacle to the discovery of new dual-target drugs. In this Perspective, we summarized the profiles concerning drug design methods, structure−activity relationships, and pharmacological parameters of dual-target drugs for the treatment of COVID-19. Importantly, we underscored how target combination and rational drug design illuminate the development of dualtarget drugs for SARS-CoV-2. ■ SIGNIFICANCE• This is the first Perspective on dual-target drugs for treating coronavirus. • Dual-target drugs, acting on multiple pathways, offer enhanced efficacy and can delay resistance compared to single-target treatments. • Drug repurposing for dual-target design can significantly shorten the timeline for clinical trials, addressing urgent medication needs during the early COVID-19 outbreak. • The introduction of covalent warheads can compensate for active site similarity issues, aiding in the development of high-affinity dual-target inhibitors.

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3-chymotrypsin-like protease in SARS-CoV-2

Al Adem,

Ferreira,

Villanueva

et al. 2024

Bioscience Reports

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Coronaviruses constitute a significant threat to the human population. Severe acute respiratory syndrome coronavirus-2, SARS-CoV-2, is a highly pathogenic human coronavirus that has caused the COVID-19 pandemic. It has led to a global viral outbreak with an exceptional spread and a high death toll, highlighting the need for effective antiviral strategies. 3-chymotrypsin-like protease (3CLpro), the main protease in SARS-CoV-2, plays an indispensable role in the SARS-CoV-2 viral life cycle by cleaving the viral polyprotein to produce eleven individual non-structural proteins necessary for viral replication. 3CLpro is one of two proteases that function to produce new viral particles. It is a highly conserved cysteine protease with identical structural folds in all known human coronaviruses. Inhibitors binding with high affinity to 3CLpro will prevent the cleavage of viral polyproteins, thus impeding viral replication. Multiple strategies have been implemented to screen for inhibitors against 3CLpro, including peptide-like and small molecule inhibitors that covalently and non-covalently bind the active site, respectively. In addition, allosteric sites of 3CLpro have been identified to screen for small molecules that could make non-competitive inhibitors of 3CLpro. In essence, this review serves as a comprehensive guide to understanding the structural intricacies and functional dynamics of 3CLpro, emphasizing key findings that elucidate its role as the main protease of SARS-CoV-2. Notably, the review is a critical resource in recognizing the advancements in identifying and developing 3CLpro inhibitors as effective antiviral strategies against COVID-19, some of which are already approved for clinical use in COVID-19 patients.

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Computational and in vitro experimental analyses of the anti-COVID-19 potential of Mortaparib and MortaparibPlus

Cited by 4 publications

References 46 publications

Exploring Potential Biomarkers and Molecular Mechanisms of Ischemic Cardiomyopathy and COVID-19 Comorbidity Based on Bioinformatics and Systems Biology

Exploring Potential Biomarkers and Molecular Mechanisms of Ischemic Cardiomyopathy and COVID-19 Comorbidity Based on Bioinformatics and Systems Biology

New Strategies for Responding to SARS-CoV-2: The Present and Future of Dual-Target Drugs

3-chymotrypsin-like protease in SARS-CoV-2

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