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

Abstract 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 EC 50 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.