Umifenovir, sold under the brand name Arbidol, is an antiviral medication 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-ei ...

and

China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's List of countries and dependencies by population, most populous country, with a Population of China, population exceeding 1.4 billion, slig ...

. The drug is manufactured by

Pharmstandard JSC Pharmstandard (russian: ПАО "Фармстандарт", PAO "Farmstandart") is a Russian multinational pharmaceutical company. It is headquartered in Dolgoprudny, Moscow Oblast. Pharmstandard's makes and exports over 400 generic and propri ...

(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 In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other c ...

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 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 ma ...

) 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 (t ...

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 virus ...

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 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 ...

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

-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

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

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 (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 herpesvir ...

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. ...

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 ...

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, consequenc ...

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 derm ...

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 Pe ...

(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 quick ...

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