Umifenovir, sold under the brand name Arbidol, is an

antiviral medication Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs d ...

for the treatment of

influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptom ...

and COVID infections used in

Russia Russia (, , ), or the Russian Federation, is a transcontinental country spanning Eastern Europe and Northern Asia. It is the largest country in the world, with its internationally recognised territory covering , and encompassing one-eigh ...

and China. The drug is manufactured by Pharmstandard (russian: Фармстандарт). It is not approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) for the treatment or prevention of influenza. Chemically, umifenovir features an

indole Indole is an aromatic heterocyclic organic compound with the formula C8 H7 N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environme ...

core, functionalized at all but one positions with different substituents. The drug has been shown in studies to inhibit viral entry into target cells and stimulate the immune response.

Status

Testing of umifenovir's efficacy has mainly occurred in China and Russia, and it is well known in these two countries. Some of the Russian tests showed the drug to be effective and a direct comparison with

oseltamivir Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at h ...

showed similar efficiency ''in vitro'' and in a clinical setting. In 2010 Arbidol was the drug brand with the highest sales volume in Russia. In the first quarter of 2020 it had a 16 percent share in the Russian antiviral market.

Mode of action

Biochemistry

Umifenovir inhibits membrane fusion of influenza virus. Umifenovir prevents contact between the virus and target host cells. Fusion between the viral envelope (surrounding the

viral capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...

) and the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the ...

of the target cell is inhibited. This prevents viral entry to the target cell, and therefore protects it from infection. Some evidence suggests that the drug's actions are more effective at preventing infections from

RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruse ...

es than infections from

DNA virus A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and ...

es. As well as specific antiviral action against both

influenza A '' A virus'' (''IAV'') causes influenza in birds and some mammals, and is the only species of the genus ''Alphainfluenzavirus'' of the virus family ''Orthomyxoviridae''. Strains of all subtypes of influenza A virus have been isolated from wild ...

and

influenza B ''Influenza B virus'' is the only species in the genus ''Betainfluenzavirus'' in the virus family ''Orthomyxoviridae''. Influenza B virus is known only to infect humans and seals. This limited host range is apparently responsible for the lack o ...

viruses, umifenovir exhibits modulatory effects on the immune system. The drug stimulates a

humoral immune response Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it inv ...

, induces

interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten t ...

-production, and stimulates the

phagocytic Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is c ...

function of macrophages.

Clinical application

A Russian packet of Arbidol capsules Umifenovir is used primarily as an antiviral treatment for influenza. The drug has also been investigated as a candidate drug for treatment of

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, ...

. More recent studies indicate that umifenovir also has ''in vitro'' effectiveness at preventing entry of

Zaire ebolavirus ''Zaire ebolavirus'', more commonly known as Ebola virus (; EBOV), is one of six known species within the genus '' Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and o ...

(Kikwit strain), Tacaribe

arenavirus An arenavirus is a bisegmented ambisense RNA virus that is a member of the family ''Arenaviridae''. These viruses infect rodents and occasionally humans. A class of novel, highly divergent arenaviruses, properly known as reptarenaviruses, have ...

and

Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is ''Human gammaherpesvirus 8'', or HHV-8 in short. Like other herpesviru ...

in mammalian cell cultures, while confirming umifenovir's suppressive effect ''in vitro'' on

Hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. F ...

and

poliovirus A poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species ''Enterovirus C'', in the family of '' Picornaviridae''. There are three poliovirus serotypes: types 1, 2, and 3. Poliovirus is composed of a ...

infection of mammalian cells when introduced either in advance of viral infection or during infection.

Side effects

Side effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

in children include sensitization to the drug. No known overdose cases have been reported and

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermat ...

are limited to people with

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...

. The is more than 4 g/kg.

Criticism

In 2007, the Russian Academy of Medical Sciences stated that the effects of Arbidol (umifenovir) are not scientifically proven. Russian media criticized lobbying attempts by

Tatyana Golikova Tatiana Alexeyevna Golikova (Russian: Татьяна Алексеевна Голикова; born 9 February 1966) is a Russian politician and economist who serves as the Deputy Prime Minister of Russia for Social Policy, Labour, Health and Pen ...

(then-Minister of Healthcare) to promote umifenovir, and the unproven claim that Arbidol can speed up recovery from flu or cold by 1.3-2.3 days. They also made claims that the efficacy of umifenovir is supported by peer-reviewed studies.

Names

Arbidol is the INN. The brand name Arbidol is known as russian: Арбидол and .

Research

, umifenovir and

darunavir Darunavir (DRV), sold under the brand name Prezista among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It is often used with low doses of ritonavir or ...

were being studied as a potential combination treatment for

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickl ...

in China.

References

External links

* {{Portal bar , Medicine Anti-influenza agents Anti–RNA virus drugs Indoles Bromoarenes Phenols Dimethylamino compounds Thioethers Ethyl esters Russian drugs Drugs in the Soviet Union