Antivirals virtual screening to SARS-CoV-2 non-structural proteins

Nunes, Vinicius Schmitz; Paschoal, Diego; Costa, Luiz Antônio S.; Santos, Hélio F. Dos

doi:10.1080/07391102.2021.1921033

Cited by 6 publications

(3 citation statements)

References 55 publications

(68 reference statements)

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“…Many studies have demonstrated that targeting the virus-specific proteins is an effective strategy for drug discovery towards developing direct-acting antivirals [16][17][18]. Based on complementary approaches using both in vitro experiments and in silico virtual screenings, many drug discoveries are initiated by exploiting the effect of natural substances, including flavonoids, on essential coronavirus enzymes as a drug target (Figure 2) [19][20][21][22][23]. While in silico approaches such as molecular dynamics and structure-based virtual screening represent some of the early steps of drug discovery, in vitro studies utilize the findings to narrow down further and experiment with the most promising compounds in cell-based or cell-free methodologies.…”

Section: Introductionmentioning

confidence: 99%

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

Kaul

Paul

Kumar

et al. 2021

IJMS

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The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.

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Section: Introductionmentioning

confidence: 99%

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

Kaul

Paul

Kumar

et al. 2021

IJMS

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“…Some researchers adopted MM/PB(GB)SA calculations to screen drugs or compounds against multiple targets of SARS-CoV-2. Nunes et al 555 docked 24 approved drugs to SARS-CoV-2 Mpro, PLpro, and the ADP ribose phosphatases of nsp3, nsp9, nsp12, nsp15, and nsp16. The MM/GBSA calculations were further performed on the top three drugs from docking tests.…”

Section: Methods and Approachesmentioning

confidence: 99%

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Gao¹,

Wang²,

Chen³

et al. 2022

Chem. Rev.

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Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus–host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component in combating coronavirus disease 2019 (COVID-19) due to their low cost, their efficiency, and the fact that they are free from safety and ethical constraints. Additionally, the mechanism that governs the global evolution and transmission of SARS-CoV-2 cannot be revealed from individual experiments and was discovered by integrating genotyping of massive viral sequences, biophysical modeling of protein–protein interactions, deep mutational data, deep learning, and advanced mathematics. There exists a tsunami of literature on the molecular modeling, simulations, and predictions of SARS-CoV-2 and related developments of drugs, vaccines, antibodies, and diagnostics. To provide readers with a quick update about this literature, we present a comprehensive and systematic methodology-centered review. Aspects such as molecular biophysics, bioinformatics, cheminformatics, machine learning, and mathematics are discussed. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are interested in the status of the field.

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“…Recently, immunocompromised 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 mucormycosis [ 10 – 13 ]. Rhizomucor, a black fungus species, causes more than 75% of cases of mucormycosis [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy of Ledipasvir and Itraconazole in the Treatment of COVID-19 Patients Coinfected with Black Fungus: An In Silico Statement

Saha¹,

Yeom

Nimse

et al. 2022

BioMed Research International

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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.

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Antivirals virtual screening to SARS-CoV-2 non-structural proteins

Cited by 6 publications

References 55 publications

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Combination Therapy of Ledipasvir and Itraconazole in the Treatment of COVID-19 Patients Coinfected with Black Fungus: An In Silico Statement

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