Here are COVID-19 Drug Therapy – Potential Options

Here are COVID-19 Drug Therapy – Potential Options

According to the information we have got from the following sources here are potential options to solve the problem of COVID-19.

Source of Information

Tim Smith, PharmD, BCPS and Tony Prosser, PharmD
Clinical Drug Information | Clinical Solutions

Information Summary

According to the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the U.S. Food and Drug Administration (FDA), there are currently no medications or vaccines proven to be effective for the treatment or prevention of the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). (1) (2) (3)


In the absence of an established treatment regimen, the China International Exchange and Promotive Association for Medical and Health Care (CPAM) issued a novel 2019 coronavirus disease (COVID-19) guideline in February 2020 with recommendations on methodology,
epidemiological characteristics, disease screening and prevention, diagnosis, treatment and control, nosocomial infection prevention and control, and disease nursing.

For the direct antiviral treatment of SARS-CoV-2, CPAM recommends the use of lopinavir; ritonavir [2 capsule (dose undefined) by mouth twice daily] in combination with nebulized alfa-interferon (5 million units in
Sterile Water for Injection inhaled twice daily). CPAM has based this recommendation on weak evidence from retrospective cohort, historically controlled studies, case reports, and case series that suggest clinical benefit of lopinavir; ritonavir in the treatment of other coronavirus infection [i.e., 2002 SARS-CoV and 2012 Middle East respiratory syndrome coronavirus (MERS-CoV)]. (4) (8) (7)


In addition to CPAM, a group of Korean physicians with experience in treating SARS-CoV-2 infected patients have developed recommendations for the treatment of COVID-19. According to these physicians, antiviral medications are not recommended for use in young, healthy patients with mild symptoms and no underlying comorbid conditions. However, treatment with lopinavir 400 mg; ritonavir 100 mg (2 tablets by mouth twice daily) or chloroquine (500 mg by
mouth twice daily) should be considered for use in older patients or patients with under underlying conditions and serious symptoms. If chloroquine is unavailable, they recommend considering use of hydroxychloroquine (400 mg by mouth once daily). Use of ribavirin and
interferon were not recommended as first-line treatments because of the risk for side effects; however, use of these medications may be considered if treatment with lopinavir; ritonavir, chloroquine, or hydroxychloroquine are ineffective.

Potential future treatment options include:

1. Remdesivir (GS-5734), an investigational nucleoside analogue:

a) Remdesivir has been administered to several hundred patients with confirmed, severe SARS-CoV-2 infections in the United States, Europe, and Japan through Expanded Access or Compassionate Use programs. (9) Compassionate Use requests must be submitted to the drug manufacturer (Gilead Science, Inc.) by the treating physician.

b) A clinical trial evaluating the efficacy of remdesivir in patients infected with SARS-CoV-2 is currently being conducted in China. Data from this trial are expected by April 2020. 

c) In preclinical trials, remdesivir has demonstrated significant activity against coronavirus and a high genetic barrier to resistance.

i) In vitro data found remdesivir exerts potent antiviral activity against a
clinical isolate of SARS-CoV-2; [half-maximal effective concentration
(EC50) = 0.77 mcgM, half-cytotoxic concentration (CC50) > 100 mcgM ,
selective index (SI) > 129.87].

ii) Data suggest remdesivir (GS-5735) inhibits activity of 2002 SARS-CoV,
MERS-CoV, and bat CoV strains that have the ability to replicate in
human epithelial cells and mediate entry via human CoV receptors.

iii) Remdesivir has shown prophylactic and therapeutic efficacy against 2002
SARS-CoV in a mouse model.

iv) Resistance mutations have not been identified.

 

2) Sofosbuvir in combination with ribavirin:

a) Data from a molecular docking experiment using the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) model identified tight binding of sofosbuvir and ribavirin to the coronavirus RdRp, thereby suggesting possible efficacy of sofosbuvir and ribavirin in treating the COVID-19 infection.

Further data will continue to emerge regarding antiviral therapy for SARS-CoV-2 as clinical data
are reported.

Therapies evaluated in human clinical trials during previous coronavirus outbreaks (2002 SARS-
CoV and MERS-CoV)

1) Lopinavir; ritonavir in conjunction with ribavirin and corticosteroids

2) Interferon alfacon-1 in conjunction with corticosteroids

Of note, the WHO currently recommends against routine use of corticosteroids in patients with SARS-CoV-2, as available data suggest corticosteroids are associated with no survival benefit and possible harm. (1) CPAM states that use of corticosteroids is controversial and should therefore be use with caution

(1) World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected https://www.who.int/publications- detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected


(2) CDC Website: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html


(3) FDA Website: https://www.fda.gov/emergency-preparedness-and-response/mcm- issues/coronavirus-disease-2019-covid-19


(4) Chu CM, Cheng VCC, Hung IFN, et al. Role of lopinavir/ritonavir in the treatment of
SARS: Initial virological and clinical findings. Thorax 2004;59(3):252–256.

(5) Loutfy MR, Blatt LM, Siminovitch KA, et al. Interferon Alfacon-1 Plus Corticosteroids in
Severe Acute Respiratory Syndrome: A Preliminary Study. J Am Med Assoc 2003;290(24):3222–3228.


(6) Peiris JSM, Chu CM, Cheng VCC, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: A prospective study. Lancet 2003;361(9371):1767–1772.


(7) Jin, Y., Cai, L., Cheng, Z. et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Military Med Res 7, 4 (2020). https://doi.org/10.1186/s40779-020-0233-6


(8) Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet Published online January 24, 2020 https://doi.org/10.1016/S0140-6736(20)30183-5


(9) Bloomberg website: https://news.bloomberglaw.com/pharma-and-life-
sciences/hundreds-of-corona-patients-allowed-to-try-gileads-ebola-drug

(10) Agostini ML, Andres EL, Sims AC, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio 2018;9(2):1–15.

(11) Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sciences Published online February 28, 2020 https://doi.org/10.1016/j.lfs.2020.117477

(12) Korea Biomedical Review website:
http://www.koreabiomed.com/news/articleView.html?idxno=7428

(13) Gao J, T Zhenxue, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in the treatment of COVID-19 associated pneumonia in clinical studies.
Biosci Trends Published online February 19, 2020
https://doi.org/10.5582/bst.2020.01047

(14) Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research
2020;30:269–271.