Drug Discovery for SARS-CoV-2 Utilizing Computer-Aided Drug Design Approaches

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense RNA virus with an unusually large genome of approximately 30 kb. It is highly transmissible and exhibits broad tissue tropism. The third most pathogenic of all known coronaviruses, severe acute respiratory syndrome coro...

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Main Authors: Jiao Guo, Yang Bai, Yan Guo, Meihua Wang, Xinxin Ji, Yang Wang
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:COVID
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Online Access:https://www.mdpi.com/2673-8112/5/3/32
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author Jiao Guo
Yang Bai
Yan Guo
Meihua Wang
Xinxin Ji
Yang Wang
author_facet Jiao Guo
Yang Bai
Yan Guo
Meihua Wang
Xinxin Ji
Yang Wang
author_sort Jiao Guo
collection DOAJ
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense RNA virus with an unusually large genome of approximately 30 kb. It is highly transmissible and exhibits broad tissue tropism. The third most pathogenic of all known coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the clinical manifestation known as coronavirus disease 2019 (COVID-19), which has resulted in the loss of millions of lives on a global scale. This pandemic has prompted significant efforts to develop therapeutic strategies that target the virus and/or human proteins to control viral infection. These efforts include the testing of hundreds of potential drugs and thousands of patients in clinical trials. Although the global pandemic caused by the SARS-CoV-2 virus is approaching its end, the emergence of new variants and drug-resistant mutants highlights the need for additional oral antivirals. The appearance of variants and the declining effectiveness of booster shots are resulting in breakthrough infections, which continue to impose a significant burden on healthcare systems. Computer-aided drug design (CADD) has been widely utilized for predicting drug–target interactions and evaluating drug safety; it is regarded as an effective tool for identifying promising drug candidates to combat SARS-CoV-2. The CADD approach aids in the discovery of new drugs or the repurposing of United States Food and Drug Administration (FDA)-approved drugs, whose safety and side effects are already well established, thus making the process more viable. This review summarizes potential therapeutic agents that target SARS-CoV-2 or host proteins critical for viral pathogenesis, as identified using CADD approaches. Additionally, this study provides insights into the common in silico methods used in CADD and their current applications in the SARS-CoV-2 drug discovery process.
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spelling doaj-art-518aeb11252e4a81a2c8f09eada34f2a2025-08-20T03:43:15ZengMDPI AGCOVID2673-81122025-02-01533210.3390/covid5030032Drug Discovery for SARS-CoV-2 Utilizing Computer-Aided Drug Design ApproachesJiao Guo0Yang Bai1Yan Guo2Meihua Wang3Xinxin Ji4Yang Wang5The Xi’an Key Laboratory of Pathogenic Microorganism and Tumor Immunity, School of Basic Medicine, Xi’an Medical University, Xi’an 710021, ChinaThe Xi’an Key Laboratory of Pathogenic Microorganism and Tumor Immunity, School of Basic Medicine, Xi’an Medical University, Xi’an 710021, ChinaSchool of Modern Post, Xi’an University of Posts and Telecommunications, Xi’an 710061, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaThe Xi’an Key Laboratory of Pathogenic Microorganism and Tumor Immunity, School of Basic Medicine, Xi’an Medical University, Xi’an 710021, ChinaThe Xi’an Key Laboratory of Pathogenic Microorganism and Tumor Immunity, School of Basic Medicine, Xi’an Medical University, Xi’an 710021, ChinaSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense RNA virus with an unusually large genome of approximately 30 kb. It is highly transmissible and exhibits broad tissue tropism. The third most pathogenic of all known coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the clinical manifestation known as coronavirus disease 2019 (COVID-19), which has resulted in the loss of millions of lives on a global scale. This pandemic has prompted significant efforts to develop therapeutic strategies that target the virus and/or human proteins to control viral infection. These efforts include the testing of hundreds of potential drugs and thousands of patients in clinical trials. Although the global pandemic caused by the SARS-CoV-2 virus is approaching its end, the emergence of new variants and drug-resistant mutants highlights the need for additional oral antivirals. The appearance of variants and the declining effectiveness of booster shots are resulting in breakthrough infections, which continue to impose a significant burden on healthcare systems. Computer-aided drug design (CADD) has been widely utilized for predicting drug–target interactions and evaluating drug safety; it is regarded as an effective tool for identifying promising drug candidates to combat SARS-CoV-2. The CADD approach aids in the discovery of new drugs or the repurposing of United States Food and Drug Administration (FDA)-approved drugs, whose safety and side effects are already well established, thus making the process more viable. This review summarizes potential therapeutic agents that target SARS-CoV-2 or host proteins critical for viral pathogenesis, as identified using CADD approaches. Additionally, this study provides insights into the common in silico methods used in CADD and their current applications in the SARS-CoV-2 drug discovery process.https://www.mdpi.com/2673-8112/5/3/32severe acute respiratory syndrome coronavirus 2coronavirus disease 2019coronavirusesviral life cycleantiviral therapycomputer-aided drug design approaches
spellingShingle Jiao Guo
Yang Bai
Yan Guo
Meihua Wang
Xinxin Ji
Yang Wang
Drug Discovery for SARS-CoV-2 Utilizing Computer-Aided Drug Design Approaches
COVID
severe acute respiratory syndrome coronavirus 2
coronavirus disease 2019
coronaviruses
viral life cycle
antiviral therapy
computer-aided drug design approaches
title Drug Discovery for SARS-CoV-2 Utilizing Computer-Aided Drug Design Approaches
title_full Drug Discovery for SARS-CoV-2 Utilizing Computer-Aided Drug Design Approaches
title_fullStr Drug Discovery for SARS-CoV-2 Utilizing Computer-Aided Drug Design Approaches
title_full_unstemmed Drug Discovery for SARS-CoV-2 Utilizing Computer-Aided Drug Design Approaches
title_short Drug Discovery for SARS-CoV-2 Utilizing Computer-Aided Drug Design Approaches
title_sort drug discovery for sars cov 2 utilizing computer aided drug design approaches
topic severe acute respiratory syndrome coronavirus 2
coronavirus disease 2019
coronaviruses
viral life cycle
antiviral therapy
computer-aided drug design approaches
url https://www.mdpi.com/2673-8112/5/3/32
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