The evolution of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants around the globe has made the coronavirus disease 2019 (COVID-19) pandemic more worrisome, pressuring the health care system and resulting in an increased mortality rate. Recent studies recognized neuropilin-1 (NRP1) as a key facilitator in the invasion of the new SARS-CoV-2 into the host cell. Therefore, it is considered an imperative drug target for the treatment of COVID-19. Hence, a thorough analysis was needed to understand the impact and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to identify novel marine natural products which could block this receptor and stop the virus entry. We discovered that the binding affinity of CMNPD10175, CMNPD10017, CMNPD10114, CMNPD10115, CMNPD10020. CMNPD10018, CMNPD10153, CMNPD10149 CMNPD10464 and CMNPD10019 were substantial during the virtual screening (VS). We further explored these compounds by analyzing their absorption, distribution, metabolism, and excretion and toxicity (ADMET) properties and structural-dynamics features. Free energy calculations further established that all the compounds exhibit strong binding energy for NRP1. Consequently, we hypothesized that these compounds might be the best lead candidates for therapeutic interventions hindering virus binding to the host cell. This study provides a strong impetus to develop novel drugs against the SARS-CoV-2 by targeting NRP1.

全球范围内新型严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变种的演变使得 2019 年冠状病毒病 (COVID-19) 的大流行更加令人担忧，给医疗保健系统带来压力，导致死亡率上升。最近的研究发现，neuropilin-1 (NRP1) 是新型 SARS-CoV-2 侵入宿主细胞的关键促进因子。因此，它被认为是治疗COVID-19的迫切药物靶点。因此，需要进行彻底的分析以了解其影响并指导新疗法的开发。在这项研究中，我们使用结构和生物分子模拟技术来识别可以阻断该受体并阻止病毒进入的新型海洋天然产物。我们发现CMNPD10175、CMNPD10017、CMNPD10114、CMNPD10115、CMNPD10020的结合亲和力。 CMNPD10018、CMNPD10153、CMNPD10149、CMNPD10464 和 CMNPD10019 在虚拟筛选 (VS) 期间含量很高。我们通过分析这些化合物的吸收、分布、代谢、排泄和毒性（ADMET）特性以及结构动力学特征，进一步探索了这些化合物。自由能计算进一步证实所有化合物都对 NRP1 表现出很强的结合能。因此，我们假设这些化合物可能是阻碍病毒与宿主细胞结合的治疗干预的最佳先导候选物。这项研究为开发针对 NRP1 的新型抗 SARS-CoV-2 药物提供了强大的动力。