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Author: Sajal Kumar Jha

Small drugs with big buzz to combat COVID-19 pandemic

Contributors : Dr. Partha Roy, Assistant Professor, Department of Pharmaceutical Technology, Adamas University

Small Drugs: The concept of small drugs originated from Richard Feynman revolutionary lecture stating “There’s Plenty of Room at the Bottom” in American Physical Society annual meeting held in California Institute of Technology on December 1959.The journey since the birth of the concept to modern day small drugs or nano-scale medicines is a fascinating one. Nowadays nanomedicines have penetrated into almost all segment of marketed therapeutics with their clinical application increasing at an explosive rate day by day. Nanomedicines today represent nano pharmaceuticals, nanoimaging agents and theragnostic with a size range of 1 to 100 nm. These small variants enjoy the spotlight of healthcare sector because of their plethora of advantages like enhanced effectiveness, site-directed drug delivery, controlled drug release, lesser side-effects, reduced dosing frequency, high patient compliance and ease of personification compared to existing marketed drugs. The newest charisma of nanomedicines is their theragnostic application where they function simultaneously in therapy and diagnostic.

Global Market Share: Due the immense opportunities of such tiny therapeutics their global market share is expected to touch 350 billion USD by 2025 with a steep CAGR of over 11%.

Virus: They are obligate intracellular parasites which associate with host cells through varying receptor-ligand interactions. Viruses are a constant global threat to the health-care sector and socioeconomic growth because of their fast spread and high morbidity/ mortality rate as they can adapt to diverse conditions by genetic mutation. Added complexities include drug resistance development, different replication stages in divergent sub-cellular compartments and diverse viral replication dynamics.

COVID-19 Pandemic: Presently the world is in a shut-down mode due to World Health Organization declared pandemic crisis caused by COVID-19 virus. COVID-19 is spherical or pleomorphic enveloped single strand RNA viruses decorated with spiky projections which provide a crown-like appearance leading to its other name “CORONA”. The viral diameter ranges from 60 nm to 140 nm and has four sub types of which the beta-type is the main culprit behind severe acute respiratory syndrome claiming millions of human lives throughout the world. In the absence of any specific anti-viral drug or vaccine the global death toll due to the virus outbreak shows steep rise while its impact on global economy is just the opposite. The two cornerstones of COVID-19 treatment are therefore supportive and symptomatic while the most important requisite is isolation to sabotage mass spread. Therefore there is a huge drive in healthcare research for search of new drugs, new drug delivery systems, drug repurposing and newer diagnostic agents to control the pandemic.

 In order to mitigate these unique challenges presented by viral infections, the best available clinical solution can be the small drugs.

Small Drugs with big buzz Why?

  1. Small drugs due to their unique nano-scale size undergo speedy entry in sub-cellular chambers, obstruct viral attachment to host cell, enhance drug bioavailability and evade drug resistance.
  2. These small drugs can be engineered so that they can deliver appropriate bioactive concentration to the targeted site for eg. a specific sub-cellular region depending on the viral replication stage and mode of action of the drug.
  3. The surface-to-volume ratio of these small drugs is quite immense which allows facile loading of antiviral drug cocktail.
  4. Additionally the drug dose required to influence biological activity when formulated as nanomedicine is extremely low.
  5. The overlapping of the features described in b, c and d helps in overcoming drug resistance and minimizes the chances of side effects in unwanted tissues and organs.
  6. During intravenous administration these small drugs can be surface modified with hydrophilic polymers such as polyethylene glycol (PEG). The surface decoration with PEG prevents opsonization of the nanomedicines which enhances their circulation in blood stream, delays reticulo-endothelial system uptake and finally leads to bioavailability enhancements.
  7. The release of the antiviral bioactive from such small drugs can be controlled and sustained for a longer period than conventional antiviral drugs. This further contributes to its clinical attractiveness as it reduces the dosing frequency and ensures better compliance from the patients.
  8. Sometimes these smartly designed small drugs can be used in combination with classical antiviral drugs to ameliorate the solubility and stability of the conventional therapeutics and assist in programmed drug release. This also has a great impact in diminishing dosing frequency and intensify patient acceptance.
  9. New technological advancements have further enriched the development of these small drugs. Nanomedicines today are designed to provide therapy and diagnostic simultaneously. This theragnostic capacity can be a useful strategic ploy against COVID-19 infection where there is an urgent need of both therapeutic and diagnostic agent to control the pandemic.

The array of unique properties presented by small drugs makes them the best possible weapons in our therapeutic arsenal to fight the COVID-19 pandemic. But one area associated to such drugs that is relatively unexplored is its impact on acute/ chronic/ long-term toxicity which needs to be investigated extensively if these small drugs are to be established as COVID-19 therapeutics.

References

  1. http://www.phy.pku.edu.cn/~qhcao/resources/class/QM/Feynman’s-Talk.pdf
  2. https://www.grandviewresearch.com/press-release/global-nanomedicine-market
  3. Singh et.al, Therapeutic Advances in Infectious Disease. 2017, Vol. 4(4) 105 –131.
  4. Nikaeen et.al, Nanomedicine (Lond.) (Epub ahead of print). 2020. doi.org/10.2217/nnm-2020-0117.
  5. Szunerits et.al, Molecules. 2015, Aug 3;20(8):14051-1481.

CONVALESCENT PLASMA THERAPY IN COVID-19 MANAGEMENT

What is COVID-19?

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, has become a major concern all over the world. The pneumonia induced by the SARS-CoV-2 is named coronavirus disease 2019 (COVID-19). 

The COVID-19 effect

By mid ofthe April, 2020, this virus has affected more than 2,258,725people worldwide and caused more than 154,381 deaths.

The COVID-19 treatment approaches

No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Number of antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies. Apart from this supportive care, such as oxygen supply in mild cases and extracorporeal membrane oxygenation for the critically ill patients. specific drugs for this disease are still being researched. 

All about Convalescent Plasma

Convalescent plasma (CP) therapy, a classic adaptive immunotherapy, has been applied to the prevention and treatment of many infectious diseases for more than one century. Over the past two decades, CP therapy was successfully used in the treatment of SARS, MERS, and 2009 H1N1 pandemic with satisfactory efficacy and safety.

Convalescent plasma refers to the liquid part of the blood from recovered COVID-19 patients. So in this therapy, blood from recovered patients, which is rich with antibodies, used to treat other sick people.

How the therapy works

In this therapy, blood is drawn from a person who has recovered from COVID-19 sickness. The serum is separated and screened for virus-neutralizing antibodies. The serum, which is rich in antibodies, is then administered to a COVID-19 patient showing severe symptoms.

The process for donating plasma is similar to donating blood and takes about an hour, according to Houston Methodist, which became the first academic medical centre in the US to transfuse donated plasma from a recovered COVID-19 patient into a critically ill patient.

Plasma donors are hooked up to a small device that removes plasma while simultaneously returning red blood cells to their bodies. Unlike regular blood donation in which donors have to wait for red blood cells to replenish between donations, plasma can be donated more frequently, as often as twice a week, it said.

This therapy is not simple to harness, primarily due to the difficulty of obtaining significant amounts of plasma from survivors. In diseases like COVID-19, where most of the patients with severe symptoms are aged, and often suffer from other medical conditions such as hypertension, diabetes, and so on, the effectiveness remains questionable.

Effectiveness of the therapy

Earlier, a study in China found the therapy effective, albeit on small sample size, in treating coronavirus patients. In this trial, a 200 ml dose of convalescent plasma was administered to 10 adult COVID-19 patients with severe symptoms. The patients witnessed significant improvement with the disappearance of the virus reported among seven patients without any severe adverse side-effects.

Through this therapy, the sick acquires only temporary passive immunization. It lasts only till the time the injected antibodies remain in the bloodstream—usually less than a week. On the other hand, a vaccine, if developed, could provide life-long immunity against the pathogen.

The good news is three critically ill COVID-19 Indian-American patients in Houston are also showing signs of recovery after they were transfused with the blood plasma from recovered patients.

As the world waits for a vaccine against COVID-19 with bated breath, it remains to be seen if this method can provide a much-needed short-cut in finding a cure.

 

References:

  1. Casadevall A, Pirofski L. The convalescent sera option for containing COVID-19. J Clin Invest, 10.1172/JCI138003.
  2. Bloch EM, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19, J Clin Invest, 10.1172/JCI138745.
  3. Shen C, Wang Z, Zhao F et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA, doi:10.1001/jama.2020.4783.
  1. Dean  CL, Hooper  JW, Dye  JM,  et al.  Characterization of Ebola convalescent plasma donor immune response and psoralen treated plasma in the United States. Transfusion. 2020. doi:1111/trf.15739.
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