The Chemistry of Antiviral Agents: A Mechanistic Review from Nucleoside Analogs to Protease Inhibitors and Their Regional Relevance

Al Ramadan, Hassan Mohammed; Al-Fardan, Feras Abdullah; Albashrawi, Ahmad Hassan; Al Rumaih, Mohammad Jaffar; Morabit, Eisa Jafar; Alharbi, Mohammed Abdullah Mohammed; Alrashed, Abdulaziz Hussain Mohammed; Almuhaini, Ahmed Mohammed; Amer Alajmi, Nada Abdulrahman; Almaymuni, Faisal Mesfer Ali; Alshehri, Abdullah Saad Abdullah; Adlan, Abdullah Ghurmullah Musharraf; Alshehri, Ali Saad Abdullah; Alshehry, Abdullh Mohammed; Alotaibi, Mohammed Amer; Alamri, Zuhair Qasem H; Alshammari, Meshail Mathel; Dakhilallah, Talal; Alshehri, Abdulrahman Abdullah Mohammed; Alshehri, Shaher Abdulhadi

doi:10.21608/ejchem.2025.418735.12261

The Chemistry of Antiviral Agents: A Mechanistic Review from Nucleoside Analogs to Protease Inhibitors and Their Regional Relevance

Articles in Press

Document Type : Review Articles

Authors

Ministry of National Guard, Saudi Arabia

10.21608/ejchem.2025.418735.12261

Abstract

Background: The continuous emergence and re-emergence of viral pathogens is a major global health concern. The foundation of successful antiviral therapeutic design rests on a thorough knowledge of chemical structure to allow drugs to selectively interfere with the life cycle of viruses without harming the host.

Aim: The review unfolds a comprehensive outline of the molecular mechanisms behind leading antiviral classes, focusing specifically on the structure-activity relationships defining their efficacy. It traces the chemical development of drugs against prevalent viruses like Hepatitis C and emerging threats like SARS-CoV-2.

Methods: A Systematic review describes how a systematic literature review was employed with methodology focused on the medicinal chemistry basis of drug design. The review is presented by drug class, with atomic-level interactions between nucleos(t)ide analogs, protease inhibitors, non-nucleoside polymerase inhibitors, integrase inhibitors, and entry inhibitors and viral targets discussed.

Results: The study confirms that antiviral activity is controlled directly by specific chemical properties. Highlights are the central role of phosphonoamidate prodrugs in nucleoside analogs, the success of transition-state mimics and macrocyclization in protease inhibitors, and intelligent utilization of metal-chelating pharmacophores for integrase inhibitors. The review illustrates how HCV curative regimens were designed rationally and based on structure, and how SARS-CoV-2 agents were rapidly developed.

Conclusion: Advancement in antiviral chemotherapy is umbilically linked with the innovative use of medicinal chemistry. Conquering resistance, specificity, and bioavailability issues still depends on deliberate design of molecules that have the ability to specifically block crucial viral processes.

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