PVX, A Host Targeted Biologic to Treat Viral Disease

Viral pathogens pose a serious threat to both animals and humans and kills or incapacitate hundreds of millions of people per year. Over the past 30 years the incidence of viral epidemics has increased several-fold due to the rapid emergence of new pathogenic viruses, most notably the SARS COVID-19 pandemic. Emerging pathogens such as Ebola, Marburg, SARS-COV-2, Zika, mPox, Chikungunya, Lassa and Paramyxoviruses like Nipah and Hendra are becoming ever-increasing threats. An urgent need exists for new antiviral therapeutics, as those marketed for human use are virus and isolate-specific and may not elicit an effective response if the virus mutates. Similarly, vaccines are also virus-specific, exhibiting resistance if the virus mutates. CYGNOS Biotech is developing a propriety antimicrobial therapeutic PVX that will be commercialized for human and veterinary clinical markets. PVX is currently manufactured by chemical modification of the protein toxin (NT3), the major protein fraction in Naja naja kaouthia snake venom. NT3 is detoxified either by oxidation or by reduction and alkylation to ultimately promote biologic activity, either antiviral or antitumor. Studies have shown that NT3 exhibit partial sequence and conformation homology to a class of innate immune factors, namely defensins. Further, the amino acid sequences of these protein toxins and defensins have been relatively conserved despite countless evolutionary challenges. This is further exemplified by the Trp 26 residue found in several defensins and neurotoxins, which appears to be a critical molecular determinant for antimicrobial activity. Both in vitro and pilot animal studies demonstrated PVX effectiveness against multiple viruses, primarily DNA and RNA enveloped viruses such as: 1) canine distemper complex disease (CDV) causing a systemic disease, 2) feline herpes virus -- URI and eye infections, 3) feline corona virus -- terminal Feline Infectious Peritonitis, and other viruses or tumors that seriously afflict animals. All animals treated by IM or IV with PVX demonstrated significant improvement without adverse events. The lyophilized drug is stored for lengthy periods of time at room temperature prior to reconstitution. PVX represents a totally new class of agnostic drugs targeting the host and has been successfully dosed at 400?g/Kg in companion animals every 24 to 48 hours for a week to a month based upon PCR results and acute symptoms. The comparative in vitro and pilot animal study outcomes between the modified NT3 and defensins also suggest their structure/ function evolutionary relationship. CYGNOS visualizes PVX as a basic platform to optimize various biologic activities dependent upon protein sequence and charge. The ability to alter the sequence and/ or charge of this protein to optimize the direct or indirect biologic functions by recombinant engineering is our goal for the Phase II grant project.