Husna, Amity University Kolkata
The novel coronavirus disease (COVID-19) pandemic represents a serious public health concern. The virus that causes COVID-19, known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has an incredibly high spreading rate. It has already infected more than 200 million people and killed over 3 million, and the numbers are still rapidly rising in April 2021. More recently, there has been a rise in the number of mutated strains of SARS-CoV-2 that have been identified globally. The mutations, especially those on the spike glycoprotein, results in its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors. This not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacy of vaccines against the mutated strains of the virus.
Like other zoonotic coronaviruses, SARS-CoV-2 binds with the receptor human angiotensin-converting enzyme II (hACE2) with its surface spike glycoprotein (S) for the cell entry and infection. Moreover, the S protein is capable of undergoing mutations all the time to optimize its binding affinity and binding mode with ACE2 receptors, which can alter its pathogenesis, virulence, and transmissibility. The spike aspartic acid–614 to glycine (D614G) is the most dominant SARS-CoV-2 mutational form globally, it showed an increased binding efficiency with ACE2 receptor during the virus infection process. Moreover, another variant of the SARS-CoV-2 virus, B.1.1.7 (also known as VOC 202012/01), was also discovered. The binding affinity of the S protein of B.1.1.7 to the hACE2 receptor is increased by 1,000 times, and it exhibits 70% more transmissible ability than the previously discovered strains of the virus.
Some strategies to fight Covid-19:
Vaccination is a very effective strategy to prevent the spread of infectious diseases by reducing morbidity and mortality. Vaccines have attracted wide attention since the outbreak of COVID-19. At present, there are over 314 SARS-CoV-2 vaccines in the world that are at the research and development stage. 89 vaccines have entered the clinical trial stage, and multiple research and development technologies are being promoted in parallel to marketing the vaccine development. Excitingly, thirteen vaccines are approved for clinical use in numerous countries including mRNA vaccines, virus-vectored vaccines, inactivated virus vaccines, and protein subunit vaccines.
The current vaccines primarily protect the host against infection by producing neutralizing antibodies specific to the surface S protein antigen. However, the efficiency of these vaccines might be limited because of the mutation of the S protein. For instance, the neutralizing activity of the serum is proven to be reduced in the volunteers who have received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines against the South Africa mutant strain (B.1.351). Thus, there’s a renewed urgency of novel strategies that would effectively and rapidly prevent the infection of SARS-CoV-2 with different mutations during this period of COVID-19.
Role of Nanocatchers (NCs) against Covid-19:
Recent studies have investigated the capability of cellular nanovesicles (NVs) to inhibit the spread of the SARS-CoV-2 virus. These nanovesicles contain the hACE2 receptor to compete with host cells for SARS-CoV-2 binding, to shield host cells from the infection of SARS-CoV-2. With hACE2 as the neutralizing NCs to protect the host from the infection of SARS-CoV-2, the hACE2 nanocatchers (NCs) were fabricated from genetically engineered human embryonic kidney 293T cells. As expected, such hACE2-containing NCs showed an excellent binding affinity to the coronavirus and it’s mutant and inhibited the usual infection ability of the virus in vitro. Moreover, since after inhalation, the effective retention of cellular NVs within the lungs is a required condition for inhibiting SARS-CoV-2 infection of the lung, the researchers attempted to seek effective mucoadhesives that can increase epithelial contact, decrease mucociliary transport rate, and eventually, maintain the retention of NCs within the lungs for an extended duration after the pulmonary drug delivery. Excitingly, it was found that the introduction of mucoadhesive excipient hyaluronic acid (HA) with high biocompatibility was able to significantly prolong the retention of NCs within the lung which also exhibits the potency of successful inhibition of SARS-CoV-2 pseudovirus in the mouse model. More importantly, NCs in the lyophilized formulation were fabricated with the help of cryoprotectant sucrose which helped to increase its feasibility of clinical use including transport and long-term storage.
In conclusion, a safe and effective inhalable hACE2-containing nanocatchers (NCs) against COVID-19 has been developed which even offers many unique benefits over the existing treatments. Some of them include:
- Overexpressed hACE2 nanocatchers could strongly challenge different viral mutations and potential viral species by competing with host cells for virus infection. Such a strategy could also be extended to other potential epidemics.
- The mucoadhesive excipient introduced in this system could significantly prolong the maintenance of NCs within the lungs along with its desirable blockade effect.
- Lyophilization with cryoprotectants endowed the NCs with long-term stability during storage without activity loss, significantly increasing the attainability of their clinical use.
- Quick and large-scale production of hACE2-containing NCs is feasible by utilizing the engineered cell line.
Therefore, nano catchers can be executed in the battle against COVID-19, especially during this urgent period when there is continuous emergence of mutated viral strains.
Also read: Function and Regulation of epigenetic modifications in Yeast
Reference: Zhang, Han, et al. “Inhalable Nanocatchers for SARS-CoV-2 Inhibition.” Proceedings of the National Academy of Sciences, vol. 118, no. 29, July 2021. www.pnas.org, doi: http://10.1073/pnas.2102957118.
- The Corrosion Prediction from the Corrosion Product Performance
- Nitrogen Resilience in Waterlogged Soybean plants
- Cell Senescence in Type II Diabetes: Therapeutic Potential
- Transgene-Free Canker-Resistant Citrus sinensis with Cas12/RNP
- AI Literacy in Early Childhood Education: Challenges and Opportunities
About the Author: Husna is an undergraduate student of BTech Biotechnology at Amity University Kolkata. She is a research enthusiast in Immunology and Immunotherapy but she has a keen interest in various other Bioscience subjects as well. She is constantly focused on improving her knowledge and laboratory skills through various internships. She is a Scientific content writer who has knowledge in diverse backgrounds of Biotechnology.
Publications:
Delta strain: Know the vaccines effective against it!
Aqsa, Jamia Millia Islamia The Delta Strain: The world has witnessed various strains of the Covid-19 virus. These strains are the Alpha, Beta, Gamma, Delta strains. These were previously known as the UK, South Africa, Brazilian, and Indian variants, respectively indicating the country of their origin. Among these, the delta variant is the deadliest mutation […]