Merck’s “New Crown Medicine” submitted its listing application for the third climax in the anti-infective field?

Author: Tang Donate

On October 11, Merck and Ridgeback announced that they have formally applied to the U.

Figure 1.

Image source: Reference 1

Nevertheless, Molnupiravir still has many problems.

1.

In the recently published Phase III clinical data, molnupiravir reduced the risk of hospitalization or death by about 50%; on the 29th day after randomization, 7.

Currently approved for the treatment of COVID-19, including Gilead Science's antiviral drug Remdesivir (Remdesivir) and Regeneron's monoclonal antibody cocktail, both therapies are administered by injection, for those who do not need to be hospitalized It is inconvenient to use for mild patients

In addition, remdesivir is the only drug of its kind approved by the U.

When SARS-CoV-2 enters the cell, the virus needs to replicate its RNA genome to form a new virus

Figure 2.

Image source: Reference 5

2.

Although the company that co-developed the compound with Ridgeback has reached a licensing agreement with five Indian generic drug manufacturers

In addition, this compound has mutagenic potential in human cells—it has the possibility of integrating itself into the DNA of human cells—and does cause safety issues

3.

AT-527 is a prodrug of a guanosine nucleotide analog developed by Atea Pharmaceuticals.
It was originally targeted at HCV RdRp and proved its safety in HCV phase 1-2 clinical trials in healthy and HCV-infected subjects
.
Recently, it was found that AT-527 is active against SARS-CoV-2 in vitro
.
It has now partnered with Roche of Basel, Switzerland to develop its compounds
.
The second phase is currently being tested in hospitalized patients with moderate COVID-19 disease (ClinicalTrials.
gov Identifier: NCT04709835)
.

Galidesivir is an adenine nucleoside analog for HCV developed by BioCryst, but it has broad-spectrum activity on RNA viruses and has been developed for the treatment of deadly filoviruses (such as Ebola virus, Marburg) Virus)
.
It has relatively weak activity against SARS-CoV and MERS-CoV in vitro, and it is planned to be tested in a small phase 2 clinical trial in Brazil
.
It is the least characteristic molecule among SARS-CoV-2 nucleoside inhibitors
.

As a leader in the pharmaceutical industry, Pfizer has been developing an antiviral drug (PF-07321332) against SARS since the early 2000s, but shelved it when the SARS epidemic subsided
.
Researchers are also currently testing a compound in pill form with a mechanism similar to the original version
.
It is currently in the phase 2/3 clinical trial phase (ClinicalTrials.
gov Identifier: NCT04960202) for the treatment of patients with initial infections
.

In China, Hisun Pharmaceuticals and Frontier Biology have also deployed new crown treatment drugs
.
Junshi Bio announced on October 4 that the company will cooperate with Wangshan Wangshui Biological Medicine Co.
, Ltd.
(hereinafter referred to as "Wangshan Wangshui") to develop oral nucleoside anti-coronavirus drug VV116.
Clinical development and industrialization work on a global scale
.

Concluding remarks

In the past 30 years, there have been two peak periods for antiretroviral therapy: the first was the approval of a large number of AIDS cocktail therapy drugs in 1996-199, and the second was the approval of a series of drugs to cure hepatitis C in 2011-2017
.
Driven by the new coronary pneumonia, new antiviral drugs may usher in the third wave of listing craze
.

Although the impact of Molnupiravir on the COVID-19 pandemic is not yet known, small-molecule anti-coronavirus oral drugs have become a new research and development hotspot
.
In the future, as people further understand the life cycle of the new coronavirus, more effective therapeutic drugs will appear
.

Reference materials:

[1] Painter, Wendy P.
, et al.
"Human safety, tolerability, and pharmacokinetics of molnupiravir, a novel broad-spectrum oral antiviral agent with activity against SARS-CoV-2.
" Antimicrobial agents and chemotherapy 65.
5 (2021): e02428-20.

[2] Fischer, William A.
, et al.
"Molnupiravir, an Oral Antiviral Treatment for COVID-19.
" medRxiv (2021).

[3] https:// -compared-to-placebo-for-patients-with-mild-or-moderat/

[4] https://clinicaltrials.
gov/ct2/show/NCT04292899?term=Remdesivir&draw=2

[5] Kabinger, Florian, et al.
"Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis.
" Nature structural & molecular biology 28.
9 (2021): 740-746.