Applications of peptide-functionalized or unfunctionalized selenium nanoparticles for the passivation of SARS-CoV-2 variants and the respiratory syncytial virus (RSV)

The SARS-CoV-2 Omicron subvariants BA.4, BA. 5 and XBB are currently causing a COVID resurgence due to their increased spreading and infectivity. These latest subvariants have been shown to be somewhat resistant to the most common vaccines even with the third dose. Moreover, it has been well documented that when patients stop taking some commercial therapies (such as Paxlovid), COVID from these variants may return and may even be more contagious. Herein, we tested unfunctionalized and functionalized selenium (Se) nanoparticles with three novel peptides (NapFFTLUFLTUTEKKKK, NapFFMLUFLMUMEKKKK, and NapFFSAVLQSGFKKKK) previously shown by themselves to passivate the Omicron SARS-CoV-2 BA.4, BA.5 and XBB variants. Se is a natural element in our diet and is well known to boost the immune system, thus, providing a complementary approach to viral infections. NapFFMLUFLMUMEKKKK showed a stronger inhibition ability at 98% for Omicron BA.4 and 96% for Omicron BA.5 after just 15 minutes in vitro. Two types of Se nanoparticles (those made chemically or biogenically by cells) were tested to passivate the new SARS-CoV-2 XBB variant. Results showed that the combination of any peptide and using either type of Se NP, the Omicron subvariant XBB was inhibited by 100% after just 15 minutes in vitro. Interestingly, the use of Se NPs alone outperformed the peptides in terms of XBB passivation. Also, in order to determine a mechanism of action, functionalizing Se nanoparticles with the NapFFSAVLQSGFKKKK peptide showed a high binding ability toward the chemotrypsin-like cysteine protease (SARS CoV-2 3CLpro). Further, as a demonstration of their versatility, these functionalized peptides also passivated the Respiratory Syncytial Virus (RSV). NapFFTLUFLTUTEKKKK and NapFFMLUFLMUMEKKKK showed in silico interactions with the fusion glycoprotein of RSV prompting in vitro RSV pseudo virus testing. Compared to the conventionally precipitated synthetic Se nanoparticles, in vitro results showed that biogenic Se functionalized with the peptides enhanced the inhibition RSV to 100% after just 15 minutes of incubation. NapFFTLUFLTUTEKKKK and NapFFMLUFLMUMEKKKK also showed no potential genotoxicity or carcinogenic effects. The peptides showed good gastro-intestinal (GI) tract absorption and bioavailability as predicted using the partition coefficient (QP logPo/w), and high-water solubility as detected by QPlogS. According to these promising results, functionalizing biogenic Se nanoparticles with these novel peptides should be further studied in vivo for the improved diagnosis, prevention, and treatment of SARS-CoV-2, RSV, and other respiratory virus infections.