Therapeutics of COVID-19: Can nanotechnology be the game changer?

The outbreak of COVID-19

Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously called 2019-nCoV). As on May 1^st, COVID-19 has caused 2,33,388 deaths out of 32,56,846 confirmed cases in 210 countries and territories. The ripple effect of COVID-19 presents an unprecedented challenge to identify effective drugs for prevention and treatment. Although, the current scenario represents no such potential therapeutic outcomes in patients with either suspected or confirmed cases of COVID-19, clinicians and researchers in all over the world have been racing to get a better understanding about SARS-CoV-2 to develop new-age therapeutic strategies.

COVID-19 and Nanoparticles: The plausible interaction

As the need of the hour is to develop a smart therapeutic agent for SARS-CoV-2, the complete understanding on the structure of the virus and their action after entering in human systems is extremely important. The COVID-19 causative agent is severe acute respiratory syndrome (SARS) virus (SARS-CoV-2) which is more contagious than the previously reported SARS-COV which was observed in 2002. SARS-COV-2, a single stranded RNA-enveloped virus, targets host cells through the binding of the glycosylated spike (S) protein to a receptor protein named as angiotensin-converting enzyme 2 (ACE2) receptor located on the surface of host cells. It is already reported that a host type 2 transmembrane serine protease, TMPRSS2, facilitates its cell entry via the S protein. The interaction between viral S protein and ACE2 on the host cell surface is of significant interest since it initiates the infection process and it is found that the affinity of SARS-CoV-2 to ACE2 is 10-20 times higher than the SARS-CoV protein. So far, no evident treatment or vaccine has been developed for the treatment of COVID-19 except for some conventionally used drugs which are previously used to improve the immune system against malaria or rheumatoid arthritis called hydroxychloroquine or tocilizumab. Nanotechnology holds great promise serving as potential game changers in the field of various diseases, especially cancer. We may hope that engineered nanoparticles with its smart architecture may find a better solution towards this pandemic. Here, I would like to mention the quote of Professor Kostas Kostarelos, chair professor of nanomedicine at the university of Manchester that “viruses are the most beautiful, smart and capable nanoparticles”! Another professor Thomas Webster from Northeastern university mentioned that they are trying to develop iron based nanoformulations which may exhibit plausible interactions with spike (S) proteins due to similar size and architecture of SARS-CoV-2 with an average diameter 125 nm. They also added that these nanoformulations can be disrupted through applying infrared light treatment like in the treatment of in cancer. Unfortunately, there is still no active solution regarding the treatment of COVID-19.

Therapeutics of COVID-19: Does nanotechnology help in therapeutic development?

Various repurposed therapeutic agents are already studied in clinical trials for COVID-19 and they are in various formulations of Chloroquine, Hydroxychloroquine, Lopinavir-Ritonavir, Arbidol or Ribavirin, Tocilizumab. These drugs have shown potential results in other chronic inflammatory diseases including HIV, malaria and rheumatoid arthritis. They may appear to block viral entry into cells by inhibiting glycosylation of host receptors, endosomal acidification and inhibition of 3-chymotrypsin protease. These agents also have immunomodulatory effects through attenuation of cytokine production and inhibition of autophagy and lysosomal activity in host cells. The use of nanoparticles in the treatment of HIV has shown promising results where Poly lactic-co-glycolic acid (PLGA) nanoparticles were used as a delivery system to Lopinavir/Ritonavir therapy. Ribavirin, the antiviral agent, has delivered with polymeric nanoparticles to treat Hepatitis C with satisfactory results. Ribavirin in combination with gold (Au) nanoparticles showed antiviral activity against measles virus. Various formulations of nanoparticles along with these drugs have been successfully tested in animal models mimicking infectious diseases. Recently, a group of researchers from Germany has shown that using their functionalized carbon nanoparticles; they inhibited the entry of SARS-CoV-2 into the host cells by interfering the function of S protein. Thus, nanoparticles could help us to win over the COVID-19 outbreak.

Figure 1: Schematic represents virus-induced host immune system response and viral processing within target cells. Proposed targets of select repurposed and investigational products are noted. ACE2, angiotensin-converting enzyme 2; S protein, spike protein; and TMPRSS2, type 2 transmembrane serine protease. (Picture taken from Reference 1)