In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates

ABSTRACTCOVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies. The DMAbs were designed to enhance in vivo expression and delivered intramuscularly to cynomolgus and rhesus macaques with a modified in vivo delivery regimen. Serum levels were detected in macaques, along with specific binding to SARS-CoV-2 spike receptor binding domain protein and neutralization of multiple SARS-CoV-2 variants of concern in pseudovirus and authentic live virus assays. Prophylactic administration was protective in rhesus macaques against signs of SARS-CoV-2 (USA-WA1/2020) associated disease in the lungs. Overall, the data support further study of DNA-encoded antibodies as an additional delivery mode for prevention of COVID-19 severe disease. These data have implications for human translation of gene-encoded mAbs for emerging infectious diseases and low dose mAb delivery against COVID-19

Coscinium fenestratum: a review on phytochemicals and pharmacological properties

Coscinium fenestratum has been used in the traditional medicine, especially in the Ayurvedic method of healing as this plant can be found vastly in the Western Ghats of India. The distribution of this plant is concentrated to the Southeast Asiaincluding Sri Lanka, India, Cambodia, Vietnam, Peninsular Malaysia, Sumatra, West Java, Borneo, Northeast of Thailand and Laos. This review is related to the phytochemicals and pharmacological effects of C. fenestratum. The major chemi- cal constituents present in this plant include alkaloids, flavonoids and steroids. The most important bio-active compound is the berberine, which is the most widely studied plant compound. This plant exerts several pharmacological effects including antidiabetic, anticancer, antibacterial, antimalarial, antioxidant, antihy- pertensive, antiulcer, neuroprotector and wound healing activities. This chapter is supported by in vitro and in vivo studies carried out from the year of 1970 to 2016, which are available from PubMed, ScienceDirect, Google Scholar and Scopus