Facing the Coronavirus with continuous mutations, researchers are working hard to develop effective and broad-spectrum anti-Coronavirus drugs and vaccines. At the end of 2021, the small molecule oral drug was approved for marketing on the strength of excellent clinical data, bringing a glimmer of hope for humanity’s victory over the epidemic. This article will continue to dwell on the research and development progress of some small molecule therapeutics.
Proxalutamide is a second-generation non-steroidal androgen receptor (AR) antagonist developed by Kintor Pharma, which can inhibit the function of androgen receptors and down-regulate the expression of ACE2 and TMPRSS2 at the transcriptional level, thereby blocking the entry of SARS-COV-2 into host cells.
On April 6, 2022, Kintor Pharma announced the phase Ⅲ clinical data of proxalutamide in mild and moderate COVID-19 patients. It’s revealed that proxalutamide significantly reduces hospitalization/mortality in subjects with high-risk factors, especially those in the middle and upper age groups. In the treatment of subjects over 50 accompanied by obesity, or those over 60 (with or without basic diseases), proxalutamide caused no hospitalization or death with the protection ratio of 100%. In addition, proxalutamide continued to greatly reduce Coronavirus load with good safety. Compared with the control group, the Coronavirus load in the proxalutamide-treated group was continuously decreased from day 3 to day 28 of administration. Throughout the trial process, the incidence of adverse events was 7.9% in the control group and 9.6% in the proxalutamide group.
VV116
VV116 is a derivative of remdesivir, but has better pharmacokinetic and pharmacodynamic characteristics in vivo. In mouse models, both VV116 and the positive control drug molnupiravir could reduce the pulmonary virus titer below the detection limit, and both showed strong efficacy. A series of preclinical safety evaluation experiments have revealed that VV116 boasts good safety and no genotoxicity. It was approved for clinical use by the Ministry of Health of Uzbekistan on December 28, 2021, for the treatment of COVID-19. In Uzbekistan, its official generic name is Renmindevir while the trade name is Mindvy.
Azvudine is an effective candidate anti-Coronavirus drug. As a novel nucleoside reverse transcriptase and coprotein Vif inhibitor, it is the first class of double-target anti-HIV drugs. The Azvudine triphosphate form can be embedded during SARS-COV-2 RNA synthesis, and inhibit the associated polymerase, ultimately leading to the termination of RNA replication and exhibiting broad-spectrum anti-virus activity.
To evaluate the efficacy and safety of azvudine in mild and moderate COVID-19 patients, a randomized, open-label, and controlled clinical trial was conducted in China. In this pilot study, 20 patients with mild and moderate symptoms were enrolled and randomly assigned to azvudine group or control group. On the fourth day after treatment, the first-time nucleic acid negative conversion rate was 30% in the control group and 100% in the azvudine group. From enrollment, the time taken for first nucleic acid negative conversion was 5.6 days for 10 patients in the control group and 2.6 days for 10 patients in the azvudine group. From initial treatment, the time taken for first nucleic acid negative conversion was 9.8 days for 10 patients in the control group and 2.5 days for 4 patients in the azvudine group. No adverse events occurred in the azvudine group, compared with 3 cases in the control group.
Currently, it is undergoing phase Ⅲ clinical trials in China, Brazil, and Russia.
FB2001
The inhibitory activity IC50 of FB2001 against SARS-COV-2 3CLpro is 0.053±0.005 μM, and the antiviral activity EC50 of FB2001 is 0.42±0.08 μM in vitro, demonstrating high activity in targeting the main protease of Coronavirus, good in vivo pharmacokinetic properties and safety in experimental animals.
In March 2021, a phase I clinical study was initiated in the United States with the preliminary results showing that FB2001 has good performance in safety.
Related Products:
| Name | CAS | Synonyms | Description |
| Proxalutamide | 1398046-21-3 | GT 0918; pruxelutamide | Proxalutamide is a non-steroidal androgen receptor (AR) antagonist with potential anti-tumor activity for the treatment of prostate cancer and breast cancer. |
| Remdesivir | 1809249-37-3 | GS-5734 | Remdesivir, an analog nucleotide inhibitor, with effectively antiviral activity in vitro against various virus. |
| Azvudine hydrochloride | 1333126-31-0 | RO-0622 hydrochloride; FNC hydrochloride | Azvudine hydrochloride is a potent nucleoside reverse transcriptase inhibitor (NRTI), with antiviral activity on HIV, HBV and HCV. |