Virtual screening of substances used in the treatment of SARS-CoV-2 infection and analysis of compounds with known action on structurally similar proteins from other viruses

Negru, Paul Andrei; Miculas, Denisa Claudia; Behl, Tapan; Bungău, Alexa Florina; Marin, Ruxandra-Cristina; Bungău, Simona

doi:10.1016/j.biopha.2022.113432

Cited by 7 publications

(3 citation statements)

References 140 publications

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“…It is also easy for people of all levels of computer knowledge to use. Using their secondary structures as a common denominator, they proposed a latent space for proteins that may be utilized to make bioactivity comparisons [77].…”

Section: Discussionmentioning

confidence: 99%

A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors

Sokouti

2023

Exploration of Targeted Anti-Tumor Therapy

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The present coronavirus disease 2019 (COVID-19) pandemic scenario has posed a difficulty for cancer treatment. Even under ideal conditions, malignancies like small cell lung cancer (SCLC) are challenging to treat because of their fast development and early metastases. The treatment of these patients must not be jeopardized, and they must be protected as much as possible from the continuous spread of the COVID-19 infection. Initially identified in December 2019 in Wuhan, China, the contagious coronavirus illness 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Finding inhibitors against the druggable targets of SARS-CoV-2 has been a significant focus of research efforts across the globe. The primary motivation for using molecular modeling tools against SARS-CoV-2 was to identify candidates for use as therapeutic targets from a pharmacological database. In the published study, scientists used a combination of medication repurposing and virtual drug screening methodologies to target many structures of SARS-CoV-2. This virus plays an essential part in the maturation and replication of other viruses. In addition, the total binding free energy and molecular dynamics (MD) modeling findings showed that the dynamics of various medications and substances were stable; some of them have been tested experimentally against SARS-CoV-2. Different virtual screening (VS) methods have been discussed as potential means by which the evaluated medications that show strong binding to the active site might be repurposed for use against SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors

Sokouti

2023

Exploration of Targeted Anti-Tumor Therapy

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“…As clinical trials on other carotenoids are limited, well-designed future RCTs are necessary to provide robust evidence on the most appropriate choice of carotenoids to support immune homeostasis and function. To identify and research the efficacy of ACE2 inhibitors, in silico techniques (such as molecular docking and virtual screening) and bibliometric analysis can be efficiently used to discover and systematically screen more carotenoids that has ACEI potentials before further the in vitro and in vivo studies [168] . Further, a range of pharmacokinetics considerations (optimal doses, upper levels of intake, bioavailability and bioaccessibility factors), the duration of administration, characterization of the efficacy of each compound, and possible side effects remain to be determined.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

The landscape of potential health benefits of carotenoids as natural supportive therapeutics in protecting against Coronavirus infection

Gao²,

Quek³

et al. 2022

Biomedicine & Pharmacotherapy

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“…Those approaches are based on the similarity principle, which states that “a compound structurally similar to active compounds will probably also be active”, with the relevant exceptions of activity and property cliffs (e.g., chemical compounds with very similar chemical structures but very different activity profiles) [ 37 , 38 ]. In particular, ligand-based VS relying on the structural similarity principles typically uses molecular fingerprints generated from two-dimensional representations to describe molecular structures and compares the structural similarity between molecules within a chemical database (e.g., screening collection) and compounds with the desired activity (e.g., reference or queries) through a similarity metric [ 39 , 40 , 41 ]. The prediction of pharmacokinetic properties at this stage allows for the selection of molecules with a better probability of success and susceptibility to optimization [ 42 , 43 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning

Juárez-Mercado,

Gómez-Hernández,

Salinas-Trujano

et al. 2024

Pharmaceuticals

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SARS-CoV-2 Main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome, which is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development. Herein, we performed a large-scale virtual screening by comparing multiple structural descriptors of reference molecules with reported anti-coronavirus activity against a library with >17 million compounds. Further filtering, performed by applying two machine learning algorithms, identified eighteen computational hits as anti-SARS-CoV-2 compounds with high structural diversity and drug-like properties. The activities of twelve compounds on Mpro’s enzymatic activity were evaluated by fluorescence resonance energy transfer (FRET) assays. Compound 13 (ZINC13878776) significantly inhibited SARS-CoV-2 Mpro activity and was employed as a reference for an experimentally hit expansion. The structural analogues 13a (ZINC4248385), 13b (ZNC13523222), and 13c (ZINC4248365) were tested as Mpro inhibitors, reducing the enzymatic activity of recombinant Mpro with potency as follows: 13c > 13 > 13b > 13a. Then, their anti-SARS-CoV-2 activities were evaluated in plaque reduction assays using Vero CCL81 cells. Subtoxic concentrations of compounds 13a, 13c, and 13b displayed in vitro antiviral activity with IC50 in the mid micromolar range. Compounds 13a–c could become lead compounds for the development of new Mpro inhibitors with improved activity against anti-SARS-CoV-2.

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Virtual screening of substances used in the treatment of SARS-CoV-2 infection and analysis of compounds with known action on structurally similar proteins from other viruses

Cited by 7 publications

References 140 publications

A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors

A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors

The landscape of potential health benefits of carotenoids as natural supportive therapeutics in protecting against Coronavirus infection

Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning

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