SARS-CoV-2 Resistance to Small Molecule Inhibitors.

IF 3.1 Q2 MICROBIOLOGY Current Clinical Microbiology Reports Pub Date : 2024-09-01 Epub Date: 2024-06-24 DOI:10.1007/s40588-024-00229-6

Uxua Modrego Lopez, Md Mehedi Hasan, Brandon Havranek, Shahidul M Islam

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Abstract

Purpose of the review: SARS-CoV-2 undergoes genetic mutations like many other viruses. Some mutations lead to the emergence of new Variants of Concern (VOCs), affecting transmissibility, illness severity, and the effectiveness of antiviral drugs. Continuous monitoring and research are crucial to comprehend variant behavior and develop effective response strategies, including identifying mutations that may affect current drug therapies.

Recent findings: Antiviral therapies such as Nirmatrelvir and Ensitrelvir focus on inhibiting 3CLpro, whereas Remdesivir, Favipiravir, and Molnupiravir target nsp12, thereby reducing the viral load. However, the emergence of resistant mutations in 3CLpro and nsp12 could impact the efficiency of these small molecule drug therapeutics.

Summary: This manuscript summarizes mutations in 3CLpro and nsp12, which could potentially reduce the efficacy of drugs. Additionally, it encapsulates recent advancements in small molecule antivirals targeting SARS-CoV-2 viral proteins, including their potential for developing resistance against emerging variants.

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SARS-CoV-2 对小分子抑制剂的抗药性。

审查的目的：与许多其他病毒一样，SARS-CoV-2 也会发生基因突变。有些变异会导致新的关注变异体（VOC）的出现，影响传播性、疾病严重程度和抗病毒药物的有效性。持续监测和研究对于理解变异行为和制定有效的应对策略至关重要，包括确定可能影响当前药物疗法的变异：最近的研究结果：Nirmatrelvir 和 Ensitrelvir 等抗病毒疗法主要抑制 3CLpro，而 Remdesivir、Favipiravir 和 Molnupiravir 则针对 nsp12，从而降低病毒载量。然而，3CLpro 和 nsp12 耐药突变的出现可能会影响这些小分子药物疗法的疗效。摘要：本手稿总结了 3CLpro 和 nsp12 的突变，这些突变可能会降低药物的疗效。此外，它还概括了针对 SARS-CoV-2 病毒蛋白的小分子抗病毒药物的最新进展，包括它们对新出现的变体产生抗药性的可能性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Clinical Microbiology Reports MICROBIOLOGY-

CiteScore

7.50

自引率

1.90%

发文量

期刊介绍： Current Clinical Microbiology Reports commissions expert reviews from leading scientists at the forefront of research in microbiology. The journal covers this broad field by dividing it into four key main areas of study: virology, bacteriology, parasitology, and mycology. Within each of the four sections, experts from around the world address important aspects of clinical microbiology such as immunology, diagnostics, therapeutics, antibiotics and antibiotic resistance, and vaccines. Some of the world’s foremost authorities in the field of microbiology serve as section editors and editorial board members. Section editors select topics for which leading researchers are invited to contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, which are highlighted in annotated reference lists. These timely reviews of the literature examine the latest scientific discoveries and controversies as they emerge and are indispensable to both researchers and clinicians. The editorial board, composed of more than 20 internationally diverse members, reviews the annual table of contents, ensures that topics address all aspects of emerging research, and where applicable suggests topics of critical importance to various countries/regions.