Inhibition of Human Cytomegalovirus Entry into Host Cells through A Pleiotropic Small Molecule

Elste, James; Kaltenbach, Dominik; Patel, Vraj R.; Nguyen, Max T.; Sharthiya, Harsh; Tandon, Ritesh; Mehta, Satish K.; Volin, Michael V.; Fornaro, Michele; Tiwari, Vaibhav; Desai, Umesh R.

Together, two independent experiments with two different types agents bearing glycoprotein gB, i.e., HCMV virus and CHO-K1 cells, exhibited almost equivalent results for 100 µM SPGG. These results are encouraging and likely support that SPGG binds to glycoprotein gB of HCMV, although its affinity is expected to be weaker (10 to 100 µM). One explanation for this is that the anti-gB antibody and SPGG do not compete ideally for the same site of binding on gB. It is possible that both competitors bind gB simultaneously, albeit in a partially competitive manner, resulting in a less robust competition. Another possibility is that SPGG mediates HCMV inhibition through multiple viral surface receptors, one of which is gB. The foundation for this expectation is that SPGG has been earlier shown to bind tightly to glycoprotein D of HSV [50, 51] . Likewise, SPGG also inhibits Chlamydia infection through binding to its cell surface receptors [66] . Finally, potential pathways that could be targeted by SPGG do exist, e.g., the engagement of one or more host cell surface receptors (e.g., PDGF-R, EGF-R, neuropilin, or others). Of the two, the latter is more likely because heparan sulfate and its mimetics are known to be pleiotropic entities. . T-test analysis was used to determine significance in (C). (****) signifies a P-value of < 0.0001.