3. Coronaviruses are a large family of viruses that are known to cause
illness ranging from the common cold to more severe diseases such as
Middle East Respiratory Syndrome (MERS) and Severe Acute
Respiratory Syndrome (SARS).
Novel coronavirus (COVID-19) was identified in 2019 in Wuhan,
China. This is a new coronavirus that has not been previously identified
in humans.
11. Severe acute respiratory syndrome coronavirus 2 targets cells through the S protein that binds to the
ACE2 receptor, replicating and assembling in target cells before being released extracellularly.
Inflammatory signaling molecules are released by infected cells and may induce organ injury through
innate and acquired immunity.
https://www.spandidos-publications.com/10.3892/etm.2021.10444
12. Angiotensin II may be involved in the pathophysiological processes of pulmonary inflammation,
pulmonary edema, pulmonary fibrosis and parenchymal cell apoptosis in ARDS. SARS-CoV2 spike
proteins may result in downregulated expression of ACE2, therefore increasing local angiotensin II levels
and aggravating lung injury.
https://www.spandidos-publications.com/10.3892/etm.2021.10444
14. There are three general strategies currently used to detect SARS-CoV-2 and to diagnose COVID-19,
namely, molecular tests based on the determination of viral RNA, antigen tests based on the
determination of viral proteins, and antibody tests based on the determination of specific antibodies
against viral proteins.
Affinity Sensors for the Diagnosis of COVID-19. https://doi.org/10.3390/mi12040390
28. Molnupiravir
• Molnupiravir (MK-4482/EIDD-2801) is an investigational, orally
administered form of a potent Ribonucleoside analog that inhibits
the replication of SARS-CoV-2, the causative agent of COVID-19.
• Molnupiravir has been shown to be active in several preclinical
models of SARS-CoV-2, including for prophylaxis, treatment, and
prevention of transmission.
• Additionally, pre-clinical and clinical data have shown Molnupiravir to
be active against the most common SARS-CoV-2 variants.
29. Mechanism of Action
Effectively impairs Coronavirus replication through unique mechanism of action
Stops Covid-19 progression at early stage
30. Pharmakinetics
Absorption
Following twice daily oral administration of 800 mg molnupiravir, the median time to
peak plasma NHC concentrations (Tmax) was 1.5 hours.
Effect of Food on Oral Absorption
In healthy subjects, the administration of a single 200 mg dose of molnupiravir with a
high-fat meal resulted in a 35% reduction in NHC peak concentrations (Cmax), AUC
was not significantly affected.
Distribution
NHC does not bind to plasma proteins.
Elimination
The effective half-life of NHC is approximately 3.3 hours. The fraction of dose
excreted as NHC in the urine was ≤3% in healthy participants.
31.
32. Phase – 1 Trial
Painter et al. Antimicrobial Agents and Chemotherapy May 2021 Volume 65 Issue 5 e02428-20
Molnupiravir was well tolerated.
Fewer than half of the subjects reported an adverse event, the incidence of
adverse events was higher following administration of placebo, and 93.3% of
adverse events were mild.
One subject discontinued early due to rash.
There were no serious adverse events, and there were no clinically significant
findings in clinical laboratory, vital signs, or electrocardiography.
Plasma exposures exceeded expected efficacious doses based on scaling from
animal models; therefore, dose escalations were discontinued before a maximum
tolerated dose was reached.
33.
34. Phase 2 dose-range finding study
Molnupiravir is the first oral, direct-acting antiviral shown to be highly effective at
reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable
safety and tolerability profile.
• Among 202 treated participants, virus isolation was
significantly lower in participants receiving 800 mg
molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p
= 0.02). At Day 5, virus was not isolated from any
participants receiving 400 or 800 mg molnupiravir,
versus 11.1% of those receiving placebo (p = 0.03).
• Time to viral RNA clearance was decreased and a
greater proportion overall achieved clearance in
participants administered 800 mg molnupiravir
versus placebo (p = 0.01).
35. Phase – 3 Trial (MOVE-OUT)
7.3%
MOLNUPIRAVIR GROUP
14.1%
PLACEBO GROUP
Fewer hospital admissions in Molnupiravir group compared to standard of care alone (7
(1.89%) Vs 23 (6.22%) p= 0.0027) over 14 days of observation.
36. Phase – 3 Trial (MOVE-OUT)
Earlier clinical improvement (2-point decrease in WHO Clinical Progression Scale) observed in
Molnupiravir group compared to standard of care (Day 5 (63.43% vs 22.33%; p=<0.0001), Day 10
(78.96% vs 49.49%; p=<0.0001) and Day 14 (81.55% vs 73.22%; p=0.0150)
0
10
20
30
40
50
60
70
80
90
Day - 5 Day - 10 Day - 15
63.43
78.96 81.55
22.33
49.49
73.22
Clinical Improvement Rate
Molnupiravir SOC
37. Phase – 3 Trial (MOVe-OUT)
Median time to clinical improvement as early as 8 days in Molnupiravir group compared
to 12 days in SOC alone group (p=0.0001)
0 2 4 6 8 10 12
Molnupiravir
SOC
8
12
Median Time to Clinical Improvement
Molnupiravir SOC
38. Phase – 3 Trial (MOVE-OUT)
Earlier SARS CoV-2 RT-PCR negativity observed in Molnupiravir group compared
standard of care (Day 5 (77.35% vs 26.07%; p=<0.0001) Day 10 (94.03% vs 57.20%;
p=<0.0001) and Day 14 (97.01% vs 85.21%; p=<0.0001)
0
10
20
30
40
50
60
70
80
90
100
Day - 5 Day - 10 Day - 15
77.35
94.03 97.01
26.07
57.2
85.21
RT-PCR negativity Rate
Molnupiravir SOC
