Institute of Biostructures and Bioimaging, Italian National Council for Research (IBB-CNR), Area di Ricerca Site and Headquarters, Via Pietro Castellino 111, 80131 Naples, Italy.
Molecules. 2023 Feb 24;28(5):2118. doi: 10.3390/molecules28052118.
Finding effective antiviral molecular strategies was a main concern in the scientific community when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 as an easily transmissible and potentially deadly β-coronavirus able to cause the coronavirus disease 19 (COVID-19), which famously led to one of the most worrying pandemics in recent times. Other members of this zoonotic pathogenic family were already known before 2019, but apart from the SARS-CoV, which was responsible of severe acute respiratory syndrome (SARS) pandemic in 2002/2003, and Middle East respiratory syndrome coronavirus (MERS-CoV), whose main impact on humans is geographically restricted to Middle Eastern countries, the other human β-coronaviruses known at that time were those typically associated with common cold symptoms which had not led to the development of any specific prophylactic or therapeutic measures. Although SARS-CoV-2 and its mutations are still causing illness in our communities, COVID-19 is less deadly than before and we are returning to normality. Overall, the main lesson learnt after the past few years of pandemic is that keeping our bodies healthy and immunity defenses strong using sport, nature-inspired measures, and using functional foods are powerful weapons for preventing the more severe forms of illness caused by SARS-CoV-2 and, from a more molecular perspective, that finding drugs with mechanisms of action involving biological targets conserved within the different mutations of SARS-CoV-2-and possibly within the entire family of β-coronaviruses-gives more therapeutic opportunities in the scenario of future pandemics based on these pathogens. In this regard, the main protease (M), having no human homologues, offers a lower risk of off-target reactivity and represents a suitable therapeutic target in the search for efficacious, broad-spectrum anti-β-coronavirus drugs. Herein, we discuss on the above points and also report some molecular approaches presented in the past few years to counteract the effects of β-coronaviruses, with a special focus on SARS-CoV-2 but also MERS-CoV.
当严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）于 2019 年底出现时，作为一种易于传播且可能致命的β-冠状病毒，能够引起 2019 年冠状病毒病（COVID-19），这是近年来最令人担忧的大流行之一，科学界主要关注的是寻找有效的抗病毒分子策略。这种人畜共患病病原体家族的其他成员在 2019 年之前已经为人所知，但除了导致 2002/2003 年严重急性呼吸综合征（SARS）大流行的 SARS-CoV 以及主要影响人类的中东呼吸综合征冠状病毒（MERS-CoV）之外，当时已知的其他人类β-冠状病毒通常与普通感冒症状有关，并未导致任何特定的预防或治疗措施的开发。虽然 SARS-CoV-2 及其突变株仍在我们的社区中引起疾病，但 COVID-19 的致命性已不如以前，我们正在恢复正常。总的来说，在过去几年的大流行之后，我们学到的主要教训是，通过运动、受自然启发的措施和使用功能性食品来保持身体健康和免疫力，是预防由 SARS-CoV-2 引起的更严重疾病的有力武器，从更分子的角度来看，发现作用机制涉及 SARS-CoV-2 不同突变体以及（可能在整个β-冠状病毒家族内）内保守的生物靶标的药物，为基于这些病原体的未来大流行提供了更多的治疗机会。在这方面，没有人类同源物的主要蛋白酶（M）提供了较低的脱靶反应风险，是寻找有效、广谱抗β-冠状病毒药物的合适治疗靶点。在此，我们讨论了上述观点，并报告了过去几年中提出的一些分子方法，以对抗β-冠状病毒的影响，特别关注 SARS-CoV-2，但也关注 MERS-CoV。
