The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.
Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS, hepatitis C and COVID-19. These protease inhibitors prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
Atazanavir, sold under the brand name Reyataz among others, is an antiretroviral medication used to treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth.
Ritonavir, sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor, though it now mainly serves to boost the potency of other protease inhibitors. It may also be used in combination with other medications to treat hepatitis C and COVID-19. It is taken by mouth. Tablets of ritonavir are not bioequivalent to capsules, as the tablets may result in higher peak plasma concentrations.
Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is almost always used in combination with other antiretroviral drugs.
Saquinavir, sold under the brand name Invirase among others, is an antiretroviral medication used together with other medications to treat or prevent HIV/AIDS. Typically it is used with ritonavir or lopinavir/ritonavir to increase its effect. It is taken by mouth.
Fosamprenavir (FPV), sold under the brand names Lexiva and Telzir, is a medication used to treat HIV/AIDS. It is a prodrug of the protease inhibitor and antiretroviral drug amprenavir. It is marketed by ViiV Healthcare as the calcium salt.
Umifenovir, sold under the brand name Arbidol, is an antiviral medication for the treatment of influenza and COVID infections used in Russia and China. The drug is manufactured by Pharmstandard. It is not approved by the U.S. Food and Drug Administration (FDA) for the treatment or prevention of influenza.
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 cobicistat to increase darunavir levels. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth once to twice a day.
Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012, for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014, the FDA approved Elvitegravir as a single pill formulation under the trade name Vitekta. On November 5, 2015, the FDA approved the drug for use in patients affected with HIV-1 as a part of a second fixed dose combination pill known as Genvoya.
Camostat is a serine protease inhibitor. Serine protease enzymes have a variety of functions in the body, and so camostat has a diverse range of uses. Camostat is approved in Japan for the treatment of chronic pancreatitis and postoperative reflux esophagitis. The oral proteolytic enzyme inhibitor has been on the market since 1985 under the trade name Foipan Tablets. The manufacturer is Ono Pharmaceutical. The drug is used in the treatment of some forms of cancer and is also effective against some viral infections, as well as inhibiting fibrosis in liver or kidney disease or pancreatitis.
Many major physiological processes depend on regulation of proteolytic enzyme activity and there can be dramatic consequences when equilibrium between an enzyme and its substrates is disturbed. In this prospective, the discovery of small-molecule ligands, like protease inhibitors, that can modulate catalytic activities has an enormous therapeutic effect. Hence, inhibition of the HIV protease is one of the most important approaches for the therapeutic intervention in HIV infection and their development is regarded as major success of structure-based drug design. They are highly effective against HIV and have, since the 1990s, been a key component of anti-retroviral therapies for HIV/AIDS.
Cobicistat, sold under the brand name Tybost, is a medication for use in the treatment of human immunodeficiency virus infection (HIV/AIDS). Its major mechanism of action is through the inhibition of human CYP3A proteins.
Lopinavir/ritonavir (LPV/r), sold under the brand name Kaletra among others, is a fixed-dose combination antiretroviral medication for the treatment and prevention of HIV/AIDS. It combines lopinavir with a low dose of ritonavir. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth as a tablet, capsule, or solution.
The 3C-like protease (3CLpro) or main protease (Mpro), formally known as C30 endopeptidase or 3-chymotrypsin-like protease, is the main protease found in coronaviruses. It cleaves the coronavirus polyprotein at eleven conserved sites. It is a cysteine protease and a member of the PA clan of proteases. It has a cysteine-histidine catalytic dyad at its active site and cleaves a Gln–(Ser/Ala/Gly) peptide bond.
Danoprevir (INN) is an orally available 15-membered macrocyclic peptidomimetic inhibitor of NS3/4A HCV protease. It contains acylsulfonamide, fluoroisoindole and tert-butyl carbamate moieties. Danoprevir is a clinical candidate based on its favorable potency profile against multiple HCV genotypes 1–6 and key mutants (GT1b, IC50 = 0.2–0.4 nM; replicon GT1b, EC50 = 1.6 nM). Danoprevir has been evaluated in an open-label, single arm clinical trial in combination with ritonavir for treating COVID-19 and favourably compared to lopinavir/ritonavir in a second trial.
Drug repositioning is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine and convalescent plasma transfusion.
COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.
Nirmatrelvir is an antiviral medication developed by Pfizer which acts as an orally active 3C-like protease inhibitor. It is part of a nirmatrelvir/ritonavir combination used to treat COVID-19 and sold under the brand name Paxlovid.
Nirmatrelvir/ritonavir, sold under the brand name Paxlovid, is a co-packaged medication used as a treatment for COVID‑19. It contains the antiviral medications nirmatrelvir and ritonavir and was developed by Pfizer. Both components are protease inhibitors: nirmatrelvir inhibits SARS-CoV-2 main protease, while ritonavir inhibits HIV-1 protease, and is additionally a strong CYP3A inhibitor. It is taken by mouth.
