Chakraborty Ashok, Diwan Anil, Arora Vinod, Thakur Yogesh, Chiniga Vijetha, Tatake Jay, Pandey Rajesh, Holkar Preetam, Holkar Neelam, Pond Bethany
Department of Biochemistry, AllExcel, Inc., 118, Wood Street, Ste 201, West Haven, CT 06516, USA.
Department of Virology, NanoViricides, Inc., 1, Controls Dr. Shelton, CT 06484, USA.
AIMS Public Health. 2022 Apr 12;9(2):415-422. doi: 10.3934/publichealth.2022028. eCollection 2022.
NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pendants. This molecular design is used to attack many strains of coronaviruses in a broad-spectrum manner. The ligand works by competitive inhibition and binds to the same site on the S-protein of SARS-CoV that attaches to the cognate cellular receptor, ACE2. This prevents SARS-CoV from binding and infecting the cell. NV-CoV-2 is designed to bind to the free virion particles at multiple points encapsulate the virus and disable its ability to infect the cells. The multi-point binding interaction, like a nano-velcro-tape, may lead to lipid-lipid fusion of the alkyl chains in the nanoviricide micelle with the lipid envelope of the virus. The virus becomes dismantled to a capsid form before the host immune system becomes involved. This putative mechanism is orthogonal to many other anti-coronavirus agents in development. Thus, it maybe possible to produce a stronger antiviral effect when combining NV-CoV-2 therapy with other anti-coronavirus therapies such as Remdesivir (RDV). NV-CoV-2 can encapsulate other antiviral compounds as well. In this study, RDV was encapsulated and protected from serum-mediated degradation . As a result, RDV was available for a longer period of time to interact with RNA polymerase and inhibit.
NV-CoV-2是一种与聚乙二醇(PEG)和烷基侧链共价结合的纳米病毒剂。这种分子设计用于以广谱方式攻击多种冠状病毒株。该配体通过竞争性抑制起作用,并与严重急性呼吸综合征冠状病毒(SARS-CoV)的S蛋白上与同源细胞受体血管紧张素转换酶2(ACE2)结合的相同位点结合。这可防止SARS-CoV结合并感染细胞。NV-CoV-2旨在在多个点与游离病毒粒子结合,包裹病毒并使其丧失感染细胞的能力。这种多点结合相互作用就像一条纳米魔术贴带,可能导致纳米病毒剂胶束中的烷基链与病毒的脂质包膜发生脂质-脂质融合。在宿主免疫系统参与之前,病毒就会解体为衣壳形式。这种假定的机制与许多其他正在研发的抗冠状病毒药物不同。因此,将NV-CoV-2疗法与其他抗冠状病毒疗法(如瑞德西韦(RDV))联合使用时,可能会产生更强的抗病毒效果。NV-CoV-2也可以包裹其他抗病毒化合物。在本研究中,RDV被包裹起来,免受血清介导的降解。结果,RDV可在更长时间内与RNA聚合酶相互作用并产生抑制作用。