NanoViricides, Inc. (OTC BB: NNVC.OB) (the "Company") reports that its anti-HIV drug candidates demonstrated efficacy in the recently completed cell culture studies using two distinctly different HIV-1 isolates. The studies were performed in the laboratory of Carol Lackman-Smith at the Southern Research Institute, Frederick, Maryland.
“We believe that our strategy of designing ligands that are close mimics of the invariant binding site on CD4 has resulted in nanoviricides that are active against multiple HIV-1 subtypes”
This in vitro or cell culture study validated the in vivo anti-HIV activity of the nanoviricides® as determined in a SCID/hu Thy/Liv mouse model by KARD Scientific, a contract research organization, and previously reported by the Company.
Significantly, a subset of the anti-HIV nanoviricides tested in cell culture models at Southern Research had very similar activity against two distinctly different isolates of HIV-1, viz. Ba-L and IIIB. The Company had designed the ligands using reported gp120 structures of several HIV-1 strains.
The HIV-1 isolate Ba-L was the same as that employed in the Company's previously reported animal model studies. This virus binds and infects cells expressing the human receptor CCR5 in addition to the well known receptor CD4. In contrast, HIV-1 IIIB is a CXCR4-tropic virus that infects cells expressing the human receptor CXCR4 in addition to the receptor CD4. The same viral gp120 or SU glycoprotein is involved in binding to both co-receptors, viz. CD4 and either CCR5 or CXCR4. HIV that binds to CD4 and to at least one other co-receptor, such as CXCR4 or CCR5, results in productive infection leading to disease, and eventually AIDS.
It has been a formidable challenge for researchers in the field to develop an anti-HIV drug that works against all subtypes and strains. Several anti-HIV drugs and drug candidates have demonstrated significant activity against only one of these various HIV-1 subtypes. In addition, HIV mutates, changing its genome and protein structure during an active infection. Mutants resistant to the patients' treatment drugs can develop and proliferate, leading to failure of therapy, including the HAART regimen.
"We believe that our strategy of designing ligands that are close mimics of the invariant binding site on CD4 has resulted in nanoviricides that are active against multiple HIV-1 subtypes," said Anil R. Diwan, PhD, President of the Company, adding, "The results of the Southern Research study suggest that mutations in HIV-1 may be unlikely to result in significant resistance to an anti-HIV nanoviricide."
The Company had provided Southern Research with a panel of seventeen substances, including active and inactive substances. The Southern Research study was performed three different times on the same set of materials with substantially consistent results. The results confirmed that the previously demonstrated in vivo anti-HIV activity of certain nanoviricides was correlated with their in vitro anti-HIV activity.
The Company has previously reported that several of its nanoviricide drug candidates were more than 25 times (2,500%) superior to a three-drug HAART cocktail in a standard SCID-hu Thy/Liv mouse model study of HIV-I infection. In particular, treatment with only 150 mg/kg nanoviricides, as opposed to 4,200 mg/kg HAART drug cocktail (i.e. 28 times greater total dosage of HAART cocktail) resulted in viral load decrease that was equal to or better than HAART, and increased double-positive CD4+/CD8+ T cell counts that were equal to or better than HAART. The nanoviricides were equal or superior to the HAART cocktail in all parameters evaluated. Significantly, the nanoviricide treatment was given only during the first week in this six-week anti-HIV study, whereas HAART treatment was continued daily.
"We are now a step closer to filing a pre-IND application for HIVCide™ with the US FDA," said Eugene Seymour, MD, MPH, CEO of the Company.
Researchers receive NIH grant to help develop gene therapy for HIV