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Record W4253075979 · doi:10.21203/rs.3.rs-103595/v1

Structural analogues of existing anti-viral drugs inhibit SARS-CoV-2 RNA dependent RNA polymerase: A computational hierarchical investigation

2020· preprint· en· W4253075979 on OpenAlexfundno aff
Md. Kamrul Hasan, Mohammad Kamruzzaman, Omar Hamza Bin Manjur, Araf Mahmud, Nazmul Hussain, Muhammad Shafiul Alam Mondal, Md. Ismail Hosen, Martiniano Bello, Atiqur Rahman

Bibliographic record

VenueResearch Square (Research Square) · 2020
Typepreprint
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsnot available
FundersUniversity of Alberta
KeywordsPolymeraseRNA polymeraseRNA-dependent RNA polymeraseRNAVirologySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)Computational biologyChemistryBiologyMedicineEnzymeBiochemistryGene

Abstract

fetched live from OpenAlex

Abstract It’s been more than 8 months since COVID-19 became a pandemic and scientists all over the world are struggling to find suitable solutions to combat it. Multiple repurposed drugs have already been in several trials or recently completed. However, none of them shows any promising effect in combating COVID-19. Therefore, developing an effective drug is an unmet global need. RdRP (RNA dependent RNA polymerase) plays a pivotal role in viral replication therefore, it is considered as a prime target of drugs that may treat COVID-19. In this study, we have screened a library of compounds, containing approved RdRP inhibitor drugs in use to treat other viruses (Favipiravir, Sofosbuvir, Ribavirin, Lopinavir, Tenofovir, Ritonavir, Galidesivir and Remdesivir) and their structural homologues, in order to identify potential inhibitors of SARS-Cov-2 RdRP. Extensive screening, molecular docking and molecular dynamics show that five structural analogues have notable inhibitory effects against RdRP of SARS-Cov-2. Importantly, comparative protein-antagonists interaction revealed that these compounds fit well in the pocket of RdRP. ADMET analysis of these compounds suggests their potency as drug candidates. Our identified compounds may serve as potential therapeutics for COVID-19.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.015
Threshold uncertainty score0.029

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.232
GPT teacher head0.464
Teacher spread0.232 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2020
Admission routes1
Has abstractyes

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