SHELTON, CONNECTICUT -- Tuesday, March 2, 2021 -- NanoViricides, Inc. (NYSE American: NNVC) (the "Company"), a leader in the development of highly effective antiviral therapies based on a novel nanomedicine technology platform, reported today on the strong pan-coronavirus effectiveness of its two COVID-19 clinical drug candidates for which the Company is preparing a pre-IND application.
NV-CoV-2 is the Company's broad-spectrum anti-coronavirus clinical lead drug candidate for the treatment of COVID-19 patients based on its nanoviricides® platform. In addition, the Company is also developing NV-CoV-2-R, a drug treatment that combines the power of both NV-CoV-2 and remdesivir in a single drug that encapsulates and protects remdesivir inside NV-CoV-2.
Both NV-CoV-2 and NV-CoV-2-R are expected to work against most, if not all, coronaviruses and their variants, based on the Company's findings on their pre-clinical effectiveness discussed below. NV-CoV-2-R is designed to attack both (1) the virus reinfection cycle outside cells, and (2) the virus replication cycle inside cells. NV-CoV-2-R is thus potentially a cure for COVID-19 infection by virtue of attacking the total virus lifecycle.
NV-CoV-2 and NV-CoV-2-R were found to be highly effective in comparison to remdesivir against two distinctly different coronaviruses in our new cell culture studies leading towards a pre-IND application and thereafter an IND submission for these COVID-19 drug candidates. Remdesivir is one of the most effective anti-coronavirus drugs in cell culture studies. Therefore our finding that NV-CoV-2 was highly effective and comparable to remdesivir in activity in these cell culture studies was pleasantly surprising. Even more striking was the finding that NV-CoV-2-R exceeded the effectiveness of remdesivir itself in these cell culture studies. These results indicate that NV-CoV-2 and NV-CoV-2-R could be some of the strongest weapons in the fight against coronaviruses and the current COVID-19 global pandemic.
The strong effectiveness of the three drugs NV-CoV-2, NV-CoV-2-R, and remdesivir against two unrelated coronaviruses (namely hCoV-NL63 and hCoV-229E) indicates their strong potential for treatment of coronavirus diseases including COVID-19, irrespective of variants or coronavirus types. The broad-spectrum effectiveness of the Company's drug candidates is very important as coronavirus variants that are reported to evade antibodies, potentially causing disease in spite of vaccination, are becoming widespread as the COVID-19 global pandemic is progressing into its second year.
Remdesivir is known to be highly effective in cell culture studies against many coronaviruses as well as Ebola and other viruses. Thus NV-CoV-2-R can be expected to be at least as effective as remdesivir against all of these viruses in cell cultures. Moreover, NV-CoV-2-R would be expected to be significantly superior to remdesivir in human clinical studies, if our encapsulation process effectively protects remdesivir from bodily metabolism as is anticipated.
Remdesivir (Veklury®, Gilead) has shown relatively weak effectiveness in clinical studies in contrast to its extremely strong effectiveness in cell culture studies. Scientists have related this to the rapid metabolism of remdesivir in the blood stream causing loss of clinical effectiveness.
The Company believes that encapsulation of remdesivir into the nanoviricide NV-CoV-2 should protect it from bodily metabolism and thereby enable strong clinical effectiveness of the combined drug NV-CoV-2-R against COVID-19 variants as well as Ebola and possibly many other viruses for the treatment of infected humans.
The Company studied the effectiveness of NV-CoV-2, NV-CoV-2-R and remdesivir against two unrelated human coronaviruses: h-CoV-229E (229E), and h-CoV-NL63 (NL63). Of these NL63 uses the same ACE2 human cell receptor to gain entry into cells as do all variants of SARS-CoV-2 and SARS-CoV-1. Additionally, human pathology of NL63 infection closely mimics that of SARS-CoV-2, albeit with limited disease severity. NL-63 is being used as a model for anti-SARS-CoV-2 drug development in various labs including ours (see Chakraborty and Diwan for a review1). In contrast, 229E uses the cell surface receptor APN for entry rather than ACE2, and causes common colds. Thus, NL63 and 229E are unrelated human coronaviruses.
The Company intends to report on the results of these studies in its pre-IND application to the US FDA to obtain guidance regarding human clinical trials for treatment of COVID-19 patients. Additionally, the Company is actively seeking opportunities to engage appropriate sites for human clinical trials. Further, the Company is engaged in the preparation of clinical trial protocols and other activities that would be necessary for submitting an IND application to the US FDA.
The Company has developed NV-CoV-2 based on its platform nanoviricides® technology. This approach enables rapid development of new drugs against a number of different viruses. A nanoviricide is a "biomimetic" - it is designed to "look like" the cell surface to the virus. The nanoviricide technology enables direct attacks at multiple points on a virus particle. It is believed that such attacks would lead to the virus particle becoming ineffective at infecting cells. Antibodies in contrast attack a virus particle at only two attachment points per antibody.
It is anticipated that when a virus comes in contact with the nanoviricide, not only would it land on the nanoviricide surface, binding to the copious number of ligands presented there, but it would also get entrapped because the nanomicelle polymer would turn around and fuse with the virus lipid envelope, harnessing a well known biophysical phenomenon called "lipid-lipid mixing". In a sense, a nanoviricide drug acts against viruses like a "venus-fly-trap" flower does against insects. Unlike antibodies that tag the virus and require the human immune system to take over and complete the task of dismantling the virus, a nanoviricide is a nanomachine that is designed to not only bind to the virus but also complete the task of rendering the virus particle ineffective.
In addition, the nanoviricide technology also simultaneously enables attacking the rapid intracellular reproduction of the virus by incorporating one or more active pharmaceutical ingredients (APIs) within the core of the nanoviricide. The nanoviricide® technology is the only technology in the world, to the best of our knowledge, that is capable of both (a) attacking extracellular virus, thereby breaking the reinfection cycle, and simultaneously (b) disrupting intracellular production of the virus, thereby enabling complete control of a virus infection.
The Company has developed NV-CoV-2-R based on this encapsulation capability that is built in its nanoviricide NV-CoV-2. The Company has chosen to encapsulate remdesivir as the participating drug for blocking the viral replication cycle. Remdesivir is approved by the US FDA for the treatment of patients hospitalized with COVID-19. Encapsulation of remdesivir in the Company's nanoviricide envelope is expected to protect it from metabolism in the body. This protection can be expected to lead to significant enhancement in the effectiveness of remdesivir itself (in the encapsulated form), by potentially increasing both the effective remdesivir concentration and the duration of action. This could be an additional favorable effect for the Company's anti-coronavirus drug candidate NV-CoV-2-R. Remdesivir is sponsored by Gilead. The Company is developing its drug candidates independently at present.
1. A. Chakraborty and A. Diwan (2020). "NL63: A Better Surrogate Virus for studying SARS- CoV-2". Integr Mol Med, 2020, vol.7, pp 1-9, doi: 10.15761/IMM.1000408.