Antivirals Recommended by Dr Nishtha Singh Saans doctor in Jaipur For more Details 09461685766

1. Antivirals 1. REMDESIVIR (Gilead) 2. FAVIPRAVIR (Fujifilm) 3. LOPINAVIR-RITONAVIR (Abbvie)

2. Remdesvir recognized as a promising antiviral drug with in-vivo inhibitory

3. What works and what doesn’t ? 1.ANTI-VIRALS 2.ANTI-INFLAMMATORY AGENTS 3.CHLOROQUINE /HYDROCHLOROQUINE 4.HUMAN CONVALESCENT PLASMA 5.VACCINES 6.AND WHAT DOESN’T WORK ?

4. Remdesivir • A 10 year old IV anti- viral discovered by Gilead Sciences • Shown then to be effective against SARS, MERS, some Corona viruses • First used in clinical trials against Ebola: 500 cases (did not prove effective) • Currently to be fast- tracked and tested in 5 COVID-19 clinical trials set up at breakneck speed: initial results soon • Safe: transient elevation in transaminases reported in phase 1 studies • Used (compassionate) in the first COVID-19 case reported in the USA

5. Favipiravir (Avigan):Fujifilm • An experimental antiviral drug: viral RNA polymerase inhibitor- • Licensed for use against Influenza in Japan since in Japan since 5 years: • Japanese Government stockpiled 2 million courses for use in seasonal influenza • Not yet FDA approved: but under Trump pressure to speed up

6. Favipiravir • Used in Ebola trials in Africa: with evidence of some effect • Used in COVID-19 patients in Wuhan and Shenzen: • Shortened fever duration from 4.2 days to 2.5 days in 340 patients and was ‘’clearly effective’’ Chinese Health Ministry (Guardian 18/3/20) • Respiratory improvement in 80 patients in Shenzhen Chen c et al medRxiv (Pre review, posted 27/3/20)

7. Favipiravir (Avigan):Fujifilm • Oral • Cheap: $ 5 a pill, $ 650 for a course • Safe • Easy to mass produce, off patent: hence generics possible: • China has already stockpiled large numbers of courses • Probably most effective in moderate cases (not severe) • Must be given early

8. Lopinavir-Ritonavir • Lopinavir : a PI used in HIV • Ritonavir : boosts half life of Lopinavir by inhibiting cytochrome P450 • The combination (Caletra) showed modest in vivo anti-viral activity against SARS-COV(the virus causing SARS) • A single clinical study showed Lopinavir-Ritonavir(400/100mg) reduced ARDS and mortality in SARS Chu CM Thorax 2004 • This is the first drug tried in the RCT in COVID-19 (SARS-C0V-2) Cao B at NEJM 2020

9. Lopinavir-Ritonavir

10. Lopinavir-Ritonavir • An urgent randomised clinical trial of efficacy of Lopinavir-ritonavir in severe COVID-19 • From the epicentre of the pandemic in Jin Yan-Tan Hospital, Wuhan • Open label, individually randomized trial Jan 18- Feb 3rd • No placebo due to the emergency of the situation

11. Inclusion criteria • Hospitalised adults— 1.COVID-19 +ve on RT-PCR 2.Pneumonia confirmed on chest imaging 3.SaO2 < 94% breathing room air or 4.PaO2/FiO2 < 300mg • Randomly assigned in a 1:1 ratio to: Lopinavir-Ritonavir (400/100mg) bid for 14 days + standard Supportive care • VS Standard care alone

12. 100 patients in each limb the median age of patients was 58 years(49 to 68 years) 60.3% of the patients were men 35% in each group received steroids

13. Lopinavir - Ritonavir: Results • Unfortunately trial results disappointing - - • No benefit in time to clinical improvement - - • No discernible effect on viral load - - • Slightly lower 28 day mortality in the Lopinavir-Ritonavir group: • 19% L-R vs 25% placebo (p =0.32) • In ordinary days insignificant: but in extra-ordinary days:6% drop ok? • Overall negative study: small numbers, standard care group sicker

14. Editorial comments • Remarkable that the trial began days after the virus was identified • The investors appropriately prioritized speed designing a trial that rapidly gave answers • This was a heroic effort as HCWs in Hubei were also providing patient care in an overwhelming epidemic and were themselves high risk for development to disease • Lindsey Baden and Eric Rubin, Editorial NEJM

15. Anti inflammatories • 1) TOCILIZUMAB (Actemra) • 2)SARILUMAB(Kevzara) • 3)HYDROXYCHLOROQUINE