Inactivation of SARS-CoV‑2 Spike Protein Pseudotyped Virus Infection Using ACE2-Tethered Gold Nanorods under Near-Infrared Laser Irradiation

Since the angiotensin-converting enzyme 2 (ACE2) protein is abundant on the surface of respiratory cells in the lungs, it has been confirmed to be the entry-point receptor for the spike glycoprotein of SARS-CoV-2. As such, gold nanorods (AuNRs) functionalized with ACE2 ectodomain (ACE2ED) act not only as decoys for these viruses to keep them from binding with the ACE2-expressing cells but also as agents to ablate infectious virions through heat generated from AuNRs under near-infrared (NIR) laser irradiation. Using plasmid containing the SARS-CoV-2 spike protein gene (with a D614G mutation), spike protein pseudotyped viral particles with a lentiviral core and green fluorescent protein reporter were constructed and used for transfecting ACE2-expressing HEK293T cells. Since these viral particles behave like their coronavirus counterparts, they are the ideal surrogates of native virions for studying viral entry into host cells. Our results showed that, once the surrogate pseudoviruses with spike protein encounter ACE2ED-tethered AuNRs, these virions are entrapped, resulting in decreased viral infection to ACE2-expressing HEK293T cells. Moreover, the effect of photothermolysis created by ACE2ED-tagged AuNRs under 808-nm NIR laser irradiation for 5 min led to viral breakdown. In summary, ACE2ED-tethered AuNRs with dual functions (virus decoy and destruction) could have an intriguing advantage in the treatment of diseases involving rapidly mutating viral species such as SARS-CoV-2.