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Invisible War And Weapons Against COVID-19

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06th-Apr-2020       
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Md. Jamal Hossain :
A mysterious novel virus, seventh member of coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known as COVID-19 has already expanded more than 190 countries all over the world. According to World Health Organization (WHO) report, it has affected more than8 lakh and killed approximately 42 thousands innocent people across the six continents till March 31, 2020. The highest rate has been reported in European region and Western Pacific region although its first spread was noticed during last week of December, 2019 in Wuhan, China. Meanwhile, WHO director general has notified this outbreak as pandemic which is escalating swiftly at an exponential rate.
Yet, no successful therapeutic options are allowed to treat this new virus, although several vaccines or monoclonal antibody based treatment options are envisaged by various scientists or researchers community to fight this outbreak. However, it is fact to bear in mind that for new inventions of drugs or vaccines, it requires long times from months to years for preclinical and clinical trials. Some bioscience scholars have proposed to repurpose some existing medications approved or under development for treating infections which are caused by hepatitis, influenza or HIV virus. One important thing is to mention the conditions based on the treatment experienced with infections occurred due to severe acute respiratory syndrome (SARS)and Middle East respiratory syndrome (MERS) as one group of scientists have proved that COVID-19 is similar to SARS coronavirus over 70% in genetic sequence.
Initially, scientists of China tried to experiment 30 existing biologically active natural drugs and Chinese traditional medicines to find out potential anti COVID-19agents. First achievement of some researchers of Shanghai Tech University of China was the development of crystal structure of the target protein, viral main proteinase (MPro) of this novel virus which regulates its replication. By utilizing this target protein, scientists have completed the virtual screenings and enzymology tests of these potential antiviral candidates. The team prognosticated that these potential therapeutic drugs can be taken into account for clinical investigation to treat Wuhan coronavirus affected patients with pneumonia.
After meanwhile, during mid-February, 2020the National Medical Products Administration of China has published a report to use Favipiravir as experimental drug to heal this pandemic illness.
Favipiravir, a nucleoside analogue which was approved for influenza, Ebola, yellow fever, chikungunya, norovirus and entervirus, can easily inhibit viral RNA synthesis and can protect host cell from RNA virus like COVID-19. Total 340 patients involved in clinical trials conducted in Wuhan and Shenzhen have proved that the drug showed its efficacy with minimal side effects. But it has been also reported that this vaccine wasn't effective for patients with more critical conditions.  
Another experimental nucleoside analogue, remdesivir has been reported as potent broad-spectrum antiviral drug against RNA viruses such as SARS and MERS in culture and animal models. A US infected patient by COVID-19 has recovered fairly by the treatment of this antiviral drug. Along with, galidesivir, is also currently in early stage of clinical trial to evaluate its safety profile, that has also exhibited its antiviral activity against RNA virus as well as SARS and MERS in preclinical studies.
A scientist of Qingdao University, JianjunGao has declared that chloroquine phosphate, used as an anti-malarial agent, showed apparent activity against COVID-19 associated with pneumonia. From a clinical trial of 100 patients, the scientist and his research colleagues have arranged a conference on February 15, 2020 and came to a decision that chloroquine phosphate has a potent activity against this novel virus with no severe side effects.
Another recommendation, which has already been most talked topic through the worldwide, a group of scientists of France confidently said in a published article, hydroxychloroquine(a derivative of chloroquine) and azithromycin showed potent activity against this anomalous virus synergistically. Although Food and Drug Administration (FDA) of USA, the country's recognition authority, is not yet to approve this for COVID-19 treatment as it needs more authentic clinical data for the desired approval and establishment of its safety profile.
A 54 year old COVID-19 infected patient has been treated with lopinavir and ritonavir combination therapy, showed significant reduction of coronavirus situation. Another recent research has been reported that treatment with this combination has failed to show any benefits in critical phase.  
The happiest news may be the beginning of the clinical trial phase I for establishment of a potential COVID-19 vaccine in Seattle, Washington with 45 participants for next 6 weeks. The vaccine will build a protein found on virus outer shell and it is the principle hope of the scientists that the formed protein will elicit an immune response against this notorious infection.
Another alarming conception was revealed from research for COVID-19 patients with hypertension as well as diabetes, as they are regular consumer of angiotensin converting enzyme inhibitors (ACEIs) like captopril, ramipril, enalapril and angiotensin type one receptor blockers (AT1RBs) like losartan, valsartan. Recently an article has been published by LANCET medical journal as these two types of drugs foment the expression of angiotensin converting enzyme-2 (ACE-2), which directly acts as carrier of COVID-19 to reach its target lung cell. Interestingly, this analysis was completely repudiated by European Society of Cardiology. They proclaimed that discontinuing these drugs may actually provoke the COVID-19 infection and highly recommended to continue these drugs until enough human data is available to establish the above sated point.
The authors of the LANCET's article also explained on augmentation of ACE-2 expression due to administration of thiazolidinediones as well as a commonly used pain killer drug ibuprofen that facilitates the COVID-19 infection. Calcium channel blockers (CCB) like verapamil, diltiazem, nifedipine, amlopdipine may be the alternatives for hypertensive patients, the article also reported. Corona virus infected patients should be prescribed only by paracetamol in place of ibuprofen another article suggested it. Although WHO is not aware of this kind of publication based on clinical and population based data. Moreover, vitamin C infusion has played vital role in reducing inflammatory conditions as well asprevention of common cold.
According to recent analysis of corona situation, the spread of this pandemic disease COVID-19 is becoming unstoppable and integrated global steps must be required to fight this unprecedented challenge. The steps adopted by China can be educative for other countries at least for this pandemic situation to rein this contagious disease, although this situation isn't same for Italy Spain or Iran.
Theoretically, we are still in safer zone than those severely affected countries by this invisible hostility. However, WHO has suggested for carrying out some aggressive approaches to overcome this public health crisis and special cares must be comprehended for older patients or who are critically ill with COVID-19 associated with cardiovascular complications.

(Md. Jamal Hossain is a Pharmacist and researcher, completed his B. Pharm and M. Pharm (Thesis) from University of Dhaka; email: jamal.du.p48@gmail.com)

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