FNC: An Advanced Anticancer Therapeutic or Just an Underdog?

Abstract

Azvudine (FNC) is a novel cytidine analogue that has both antiviral and anticancer activities. This minireview focuses on its underlying molecular mechanisms of suppressing viral life cycle and cancer cell growth and discusses applications of this nucleoside drug for advanced therapy of tumors and malignant blood diseases. FNC inhibits positive-stand RNA viruses, like HCV, EV, SARS-COV-2, HBV, and retroviruses, including HIV, by suppressing their RNA-dependent polymerase enzymes. It may also inhibit such enzyme (reverse transcriptase) in the human retrotransposons, including human endogenous retroviruses (HERVs). As the activation of retrotransposons can be the major factor of ongoing cancer genome instability and consequently higher aggressiveness of tumors, FNC has a potential to increase the efficacy of multiple anticancer therapies. Furthermore, FNC also showed other aspects of anticancer activity by inhibiting adhesion, migration, invasion, and proliferation of malignant cells. It was also reported to be involved in cell cycle arrest and apoptosis, thereby inhibiting the progression of cancer through different pathways. To the date, the grounds of FNC effects on cancer cells are not fully understood and hence additional studies are needed for better understanding molecular mechanisms of its anticancer activities to support its medical use in oncology.

Azvudine reduces the mortality rate of patients with Coronavirus disease 2019: a single-center retrospective analysis study

“…Azvudine is an RNA-dependent RNA polymerase inhibitor that primarily accumulates in the thymus and peripheral mononuclear cells, promotes immune responses, and inhibits the replication of SARS-CoV-2, thereby reducing lung tissue damage. [9][10] Azvudine is primarily approved for the treatment of all clinical types of COVID-19. [11] However, long-term e cacy data for azvudine treatment in patients with COVID-19 are lacking from real-world studies.…”

Small molecules in the treatment of COVID-19

“… 294 Azvudine is a cytosine analog which was also found to be efficient to treat SARS-CoV-2. 295 It was previously approved for HIV inhibition. 296 Recently, Zhang et al observed that azvudine significantly inhibited viral load, promoted lymphocyte subsets, protected histological structures, and reduced inflammation caused by SARS-CoV-2 infection.…”

A Comparison of Etiology, Pathogenesis, Vaccinal and Antiviral Drug Development between Influenza and COVID-19

“…For example, the small molecule oral drugs PAXLOVID and Molnupiravir have been recommended clinically because they significantly reduce the risk of hospitalization and incidence of severe illness or death following early use [ 184 , 185 , 186 ]. Another small molecule oral drug Azvudine, approved in China, has presented significant efficiency for COVID-19, although its antiviral mechanism is still unclear [ 187 ]. In addition, traditional Chinese medicine is believed to have played an important role in COVID-19 pandemic control in China.…”