Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease CO­VID-19 has strongly encouraged the search for antiviral compounds. Most of the evaluated drugs against SARS-CoV-2 derive from drug repurposing of Food and Drug Administration-approved molecules. These drugs have as target three major processes: (1) early stages of virus-cell interaction, (2) viral proteases, and (3) the viral RNA-dependent RNA polymerase. Summary: This review focused on the basic principles of virology and pharmacology to understand the importance of early stages of virus-cell interaction as therapeutic targets and other main processes vital for SARS-CoV-2 replication. Furthermore, we focused on describing the main targets associated with SARS-CoV-2 antiviral therapy and the rationale of drug combinations for efficiently suppressing viral replication. Key Messages: We hypothesized that blocking of both entry mechanisms could allow a more effective antiviral effect compared to the partial results obtained with chloroquine or its derivatives alone. This approach, already used to achieve an antiviral effect higher than that offered by every single drug administered separately, has been successfully applied in several viral infections such as HIV and HCV. This review will contribute to expanding the perception of the possible therapeutic targets in SARS-CoV-2 infection and highlight the benefits of using combination therapies.
Intervirology

中文翻译：

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了解严重急性呼吸系统综合症冠状病毒 2 的复制以设计有效的药物组合疗法

背景：严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 及其疾病 COVID-19 的出现强烈鼓励人们寻找抗病毒化合物。大多数接受评估的抗 SARS-CoV-2 药物均源自食品和药物管理局批准的分子的药物再利用。这些药物以三个主要过程为目标：(1) 病毒与细胞相互作用的早期阶段，(2) 病毒蛋白酶，以及 (3) 病毒 RNA 依赖性 RNA 聚合酶。摘要：本综述重点关注病毒学和药理学的基本原理，以了解病毒与细胞相互作用的早期阶段作为治疗靶点的重要性以及对 SARS-CoV-2 复制至关重要的其他主要过程。此外，我们重点描述了与 SARS-CoV-2 抗病毒治疗相关的主要靶点以及有效抑制病毒复制的药物组合的基本原理。关键信息：我们假设，与单独使用氯喹或其衍生物获得的部分结果相比，阻断这两种进入机制可以产生更有效的抗病毒作用。这种方法已被用来实现比单独施用每种药物所提供的抗病毒效果更高的效果，并已成功应用于多种病毒感染，例如 HIV 和 HCV。该综述将有助于扩大对 SARS-CoV-2 感染可能治疗靶点的认识，并强调使用联合疗法的好处。
病毒间学