An Intranasal Nanomedicine Functions as Both Potent Broad-spectrum Viral Inhibitor and Quasi-Vaccine

Antivirals that exert rapid inhibition and vaccines that provide long-term prevention are both of paramount importance for the intervening against fatal viral infections. Clearly, it will be highly desirable to integrate the two strategies into a single antiviral agent; however, such a concept is challenging to achieve and has not been explored yet. Herein, an unprecedented broad-spectrum antiviral photothermal nanomedicine is reported with unique advantages to offer both rapid protection and vaccine-like prevention. This nanomedicine is a rationally engineered photothermal gold nanorod capable of targeting the glycan-shield of various viruses and exerting multiple unparalleled antiviral mechanisms, i.e., blocking virus-cell attachment, inducing viral aggregation, enhancing macrophage phagocytosis, promoting virions lysis, and initiating immune response. As such, it exhibits potent and broad-spectrum antiviral efficacy toward a variety of viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its major variants, lassa virus (LASV) and porcine deltacoronavirus (PDCoV), with EC₅₀ value as low as tens of pM level and nearly 100% inhibition rate. Significantly, in vivo intranasal administration against authentic PDCoV virus challenge demonstrates rapid virus killing, effective inflammation suppression and production of protective IgA and IgG. Thus, as a proof-of-concept, this study provides new insights and evidences for the design of “two-way player” antiviral agents that can simultaneously treat and prevent viral infections.