Ebenezer O, Jordaan M A, Ogunsakin R E, Shapi M
Faculty of Natural Science, Department of Chemistry, Mangosuthu University of Technology, South Africa.
Discipline of Public Health Medicine, College of Health Sciences, University of KwaZulu Natal Durban, South Africa.
Hippokratia. 2020 Jul-Sep;24(3):99-106.
Due to the migratory flow of infected people with severe acute respiratory syndrome virus (SARS COV-2), the number of confirmed cases of coronavirus disease 2019 (COVID-19) is accelerating globally; preclinical evidence of antiviral agents that can combat this pandemic is still elusive. We identified published articles on SARS-COV efficacy experiments in which some selected compounds were used to test the reduction of the virus load in mice.
A systematic search of articles was conducted in PubMed, Web of Science, and Scopus. We then developed a combined model based on a systematic review, meta-analyses, and molecular docking studies to evaluate the effect size of preclinical studies of compounds that have been tested against SARS-COV. Because substantial heterogeneity was expected, random effect model meta-analyses were carried out to estimate the overall pooled disease's prevalence. All meta-analyses were performed with Stata version 15.0. Subgroup analyses on therapies were conducted as well. Molecular docking studies of the inhibitors in the active pocket of COVID-19 protease were also performed.
From all screened articles, six studies were appropriate for ultimate meta-analysis and systematic review. The residual amount of heterogeneity was high (τ =0.02; heterogeneity I =85.5 % with heterogeneity chi-square =103.57, a degree of freedom =15, and p <0.001). The overall random pooled prevalence of infected mice treated with the selected compounds was 78.1 % [95 % Confidence Interval (CI): 14.7-17.0 %]. Prophylactic has a significantly higher pooled prevalence than therapeutic, with 21.8 % (95 % CI: 16.4 % to 28.8 %). Our results indicated that most of the SARS-COV inhibitors analyzed were less effective in reducing the lung virus titer of SARS-COV infection in animal models. The findings from molecular docking studies also identified COVID-19 inhibitors that are good for optimization and drug development to fight against COVID-19 infection.
Findings from the review showed that studies on the preclinical compounds targeting SARS-COV and COVID-19 are limited. Furthermore, molecular docking studies and meta-analysis results substantiated three compounds, i.e., EIDD-2801, GS-5734, and amodiaquine. HIPPOKRATIA 2020, 24(3): 99-106.
由于感染严重急性呼吸综合征病毒（SARS COV - 2）的人群的迁移流动，2019冠状病毒病（COVID - 19）的确诊病例数在全球范围内加速增长；能够对抗这一疫情的抗病毒药物的临床前证据仍然难以捉摸。我们检索了已发表的关于SARS - COV疗效实验的文章，其中一些选定的化合物被用于测试小鼠体内病毒载量的降低情况。
在PubMed、科学网和Scopus上对文章进行系统检索。然后，我们基于系统评价、荟萃分析和分子对接研究开发了一个综合模型，以评估针对SARS - COV进行测试的化合物的临床前研究的效应大小。由于预计存在实质性异质性，因此进行随机效应模型荟萃分析以估计总体合并疾病的患病率。所有荟萃分析均使用Stata 15.0版本进行。还对治疗方法进行了亚组分析。此外，还对COVID - 19蛋白酶活性口袋中的抑制剂进行了分子对接研究。
在所有筛选的文章中，六项研究适合进行最终的荟萃分析和系统评价。异质性的剩余量很高（τ = 0.02；异质性I = 85.5%，异质性卡方 = 103.57，自由度 = 15，p < 0.001）。用选定化合物治疗的感染小鼠的总体随机合并患病率为78.1%[95%置信区间（CI）：14.7 - 17.0%]。预防性治疗的合并患病率显著高于治疗性治疗，为21.8%（95% CI：16.4%至28.8%）。我们的结果表明，所分析的大多数SARS - COV抑制剂在降低动物模型中SARS - COV感染的肺病毒滴度方面效果较差。分子对接研究的结果还确定了对对抗COVID - 19感染的优化和药物开发有益的COVID - 19抑制剂。
综述结果表明，针对SARS - COV和COVID - 19的临床前化合物的研究有限。此外，分子对接研究和荟萃分析结果证实了三种化合物，即EIDD - 2801、GS - 5734和阿莫地喹。《希波克拉底》2020年，24(3)：99 - 106。
