Medichealthy The Roles of Choloroquine and Remdesivir in Treatment of Coronavirus Disease 2019 - Medichealthy The Roles of Choloroquine and Remdesivir in Treatment of Coronavirus Disease 2019

The Roles of Choloroquine and Remdesivir in Treatment of Coronavirus Disease 2019

Coronavirus Disease 2019 also called Wuhan Coronavirus disease is an acute respiratory syndrome that is caused by Novel Corona-2019, a member coronavirus family. Chloroquine phosphate and Remdesivir can be used to treat emerging the COVID-19 disease caused by the Novel Corona-2019 (2019-nCoV) virus. Both of these drugs have been known to have a positive impact on other Coronavirus infections cases such as SARS-CoV and MERS-CoV.

The World Health Organization (WHO) reported an outbreak in Wuhan, China in early February 2020, since then, the coronavirus has spread to various countries. Based on data available so far, the coronavirus mortality rate has reached 2%. Symptoms of coronavirus infection resemble flu-like symptoms. However, in some cases, such as patients with comorbidities and older people,  mild complaints can develop into pneumonia or Acute Respiratory Distress Syndrome (ARDS).

The Roles of Choloroquine and Remdesivir in Treatment of Coronavirus Disease 2019


As an emerging disease, there is no specific treatment for COVID-19. Most patients only have mild flu-like symptoms. The medical treatment for patients with pneumonia or ARDS is supportive. These treatments including supplemental oxygen administration with an oxygen saturation target above 90%, conservative administration of fluid if there is no evidence of shock, and administration of empirical antimicrobial that follows community pneumonia management guidelines (Community-acquired pneumonia). Some drugs have been tried as a therapy for COVID-19, including chloroquine phosphate and some antiviral drugs such as Remdesivir.

Chloroquine Phosphate as COVID-19 Therapy

Chloroquine phosphate is widely known as an antimalarial agent. The antiviral activity of chloroquine is found for the Human Immunodeficiency (HIV) and SARS-CoV viruses. Research on chloroquine as an antiretroviral in vitro that chloroquine works by inhibiting the glycosylation of viral particles and is specific to the replication of HIV.

Choloroquine Phosphate for Wuhan Coronavirus
Chloroquine phosphate Tablet


The mechanism of action of Chloroquine Phosphate

Increasing endosomal pH and inhibition of glycosylation as the mechanism of action of Chloroquine in inhibiting the replication of SARS-CoV in vitro. With the inhibition of glycosylation, it is possible to have a specific interaction between Chloroquine and glucosyltransferase. ACE2 is a component of the SARS-CoV surface that mediates the entry of the virus to cells through bonding with protein S (spikes). ACE2 inhibition is the Chloroquine's action target.

Sialic acid is one of the virus components, which is associated with glycoproteins and gangliosides. Viruses use sialic acid as a receptor to enter cells. Viruses that use this component are corona, influenza, parainfluenza, mumps, rota, and DNA-tumor viruses. In vivo, Chloroquine also has an effect of modulating immune synergies with its antiviral action.

Chloroquine action on SARS-CoV inhibition in culture, evidenced by Real Time Polymerase Chain Reaction (RT-PCR) in the phase before infection, after initiation and infection. Therefore, Chloroquine has clinical advantages as a prophylactic and therapeutic drug. Until now, clinical trials on Chloroquine for COVID-19 from various cities in China are still ongoing. The effective concentration value of 90% of Chloroquine for 2019-nCoV on Vero E6 cells is 6.90 μM, which was found in the administration of 500 mg chloroquine in patients with rheumatoid arthritis.

Antivirals Remdesivir for COVID-19 Therapy

Antiviruses that have been studied for the management of the Coronavirus include Ribavirin (RBV), Lopinavir (LPV) -Ritonavir (RTV), Remdesivir (RDV), Nelfinavir, Arbidol, and nitric oxide gas (NO). Antiviruses such as Arbidol, Nelfinavir, and RBV combined with interferon-beta, were found to work synergistically to inhibit the replication of the SARS-CoV virus. The combination of LPV-RTV, along with RBV, was found to improve the outcome of SARS. NO gas, which can inhibit the synthesis of viral proteins and RNA (Ribonucleic Acid), has also been found to inhibit the replication of SARS-CoV.

Remdesivir

Remdesivir is one of the antiviral agents that has been used and produced good outcomes, was tried in 2019-nCoV. Remdesivir is a broad-spectrum antiviral and is an analog of adenosine that can interfere with the RNA chain of the Coronavirus. It may work by making lethal mutagenesis, terminating obligate or nonobligate chains, and inhibiting nucleotide biosynthesis. The results of the inhibition of viral RNA replication occur dose-dependent. RDV causes premature termination of RNA transcription in MERS-CoV, Ebola virus, Nipah virus, and RSV (Respiratory Syncytial Virus). The combination of RDV with interferon-beta was found to have a more superior effect than the combination of LPV and RTV, with more suppression of the replication activity of MERS-CoV. Warren's research found that administering remdesivir at a dose of 10 mg per kilogram of body weight was found to be 100% protection against the Ebola virus, which is an RNA virus just like the Coronavirus.

In a COVID-19 case report from the United States, RDV was used on the 11th day in the course of the disease where the patient's condition was worsening. There were reported improvements in clinical outcomes that were found thereafter (12th day onwards). There is no mention of the dose given in this case report.

The effective concentration value of 90% Remdesivir against 2019-nCoV in Vero E6 cells is 1.76 μM, according to the value found in nonhuman primates. RDV clinical trials for their effectiveness against COVID-19 are currently underway in the United States and China. In clinical trials in the United States, Remdesivir used was 200 mg of intravenous redemsivir on the first day and continued with a daily dose of 100 mg until the 10th day (ClinicalTrial.gov clinical trial number: NCT04280705). The effectiveness of evidence-based medicine still needs to be explored further.

Source: Alomedika
Source pict: https://www.advacarepharma.com/en/antimalarials/chloroquine-phosphate-tablets
Writer: dr. Nathania S. Sutisna


References
1. World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report – 31. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200220-sitrep-31-covid-19.pdf. Accessed: 27-February 2020.
2. World Health Organization. Interim guidance: Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected. Available from: https://www.who.int/docs/default-source/coronaviruse/clinical-management-of-novel-cov.pdf?sfvrsn=bc7da517_2. Accessed: 27-February 2020
3. Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. The Lancet infectious diseases. 2006 Feb 1;6(2):67-9.
4. Zhang L, Liu Y. Potential Interventions for Novel Coronavirus in China: A Systematic Review. Journal of medical virology. 2020.
5. Matrosovich M, Herrler G, Klenk HD. Sialic acid receptors of viruses. InSialoGlyco Chemistry and Biology II 2013 (pp. 1-28). Springer, Cham.
6. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research. 2020 Feb 4:1-3.
7. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virology journal. 2005 Dec 1;2(1):69.
8. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. BioScience Trends. 2020.
9. Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng JY, Jordan R, Ray AS. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio. 2018 May 2;9(2):e00221-18.
10. Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, Montgomery SA, Hogg A, Babusis D, Clarke MO, Spahn JE. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nature Communications. 2020 Jan 10;11(1):1-4.
11. Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, Siegel D, Perron M, Bannister R, Hui HC, Larson N. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016 Mar;531(7594):381-5.
12. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G. First case of 2019 novel coronavirus in the United States. New England Journal of Medicine. 2020 Jan 31.
13. National Institute of Health. NIH clinical trial of remdesivir to treat COVID-19 begins. Available from: https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins . Accessed: 27-February 2020.

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