**6.1 Anti-Herpes drugs**

The recognition of acyclovir and penciclovir has leaded the way evolution of a fortunate systemic therapy for medicating herpes simplex virus infection. Acyclovir is a nucleotide analogue antiviral which is used to treat against herpes simplex. It is generally used as the first line drug in the treatment viruses. Acyclovir is converted into acyclovir monophosphate due to the action of viral thymidine kinase. Acyclovir monophosphate is further converted to the diphosphate form by guanylate kinase. Acyclovir diphosphate is become acyclovir triphosphate by help of nucleoside diphosphate kinase. Acyclovir triphosphate effectively binds to viral DNA polymerase than cellular DNA polymerase and enters into DNA where 2′ and 3′ carbon leads to DNA chain termination. Acyclovir stronger affinity for viral DNA polymerase did not allow other bases to bind it, making them inactive [20].

Dose and Preparation: 200 mg 5 times a day oral (15 mg/kg/day), 5–10 mg/kg 8 hourly by slow i.v. infusion, 5% topical application 6 times a day; ZOVIRAX 200 mg tab, 250 mg/vial for i.v. injection; CYCLOVIR 200 mg tab, 5% skin cream; HERPEX 200 mg tab, 3% eye ointment, 5% skin cream; OCUVIR 200, 400, 800 mg tab, 3% eye ointment, ACIVIR-DT 200, 400, 800 mg tab.

Toxicity: Symptoms of overdose include agitation, coma, seizures, lethargy, and precipitation in renal tubules. These symptoms are more unsophisticated in patients given high doses without monitoring of fluid and electrolyte balance or reduced kidney function.

## **6.2 Anti-influenza virus drugs**


Dose and Preparation: Therapeutic Dose 10 Mg Bd By Inhalation; Prophylactic Dose 10 Mg Od; Relenza 5 Mg Per Actuation Powder Inhaler.

Toxicity: The toxicology studies illustrated that zanamivir has very little toxicity and no drug-specific toxicities were observed in animal toxicity studies.

Arbidol which is popularly used to cure influenza is reported to inhibit SARS-CoV-2 [22]. Similarly, Favipiravir, an anti-influenza drug, also is undergoing clinical trials against COVID19 [23].

#### **6.3 Anti-hepatitis virus drugs**

To date, two classes of antiviral drugs have been accepted by the Food and Drug Administration for the treatment of hepatitis B, and nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [TDF] and for hepatitis C, immunomodulators (interferon [IFN]-α and pegylated-interferon [PEG-IFN]-α). Lamivudine, a synthetic nucleoside analogue, is phosphorylated intracellularly to lamivudine triphosphate, 5′-triphosphate metabolite. The nucleoside analogue is inserted into viral DNA by HBV polymerase and HIV reverse transcriptase leading to DNA chain termination. Interferons are glycoproteins synthesized by host cells in response to viral infection and some other inducers. These are effective against DNA and RNA virus and have a no-specific inhibitory effect on the viral replication against a wide variety of unrelated viruses [24].

Dose and Preparation: For Chronic Hepatitis B 100 Mg Od; For Hiv Infection 150 Mg Bd (Along With Other Antiretroviral Drugs); Lamivir 150 Mg Tab, 150 Mg/5 Ml Solution; Lamivir-Hbv 100 Mg Tab; Heptavir, Lamidac, Lamuvid 100, 150 Mg Tabs.

Toxicity: The most common reported adverse reactions in adults were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough etc.

Remdesivir which was developed to treat Hepatitis C has also demonstrated antiviral activity against SARS-CoV-2 [25]. As per results of controlled, randomized clinical trials, remdesivir has shortened the time of recovery in adults employed to treat hospitilized COVID-19 patients [26–30]. However, remdesivir potential against new SARS-CoV-2 variants is under trail and should be monitored.

Ribavirin used to cure COVID-19 [31] approved to cure respiratory syncytial virus and HCV leads to anemia at higher dose [32]. Ribavirin is administered intravenously at a dose of 500 mg, 2–3 times a day [33].

Some Antiretroviral Combinations:


### **7. Mechanism of action of retroviral drugs.**

#### **7.1 Nucleoside reverse transcriptase inhibitors (NRTIS)**

The nucleotide/nucleoside reverse transcriptase inhibitors are the first class of antiretroviral drugs approved by FDA. NRTIS are taken up by host cells and phosphorylated and activated by cellular kinases. NRTIS lack 3′-hydroxyl group at the 2'deoxyribosyl moiety and have nucleotide/nucleoside as base. They prevent the *Role of Anti-Viral Drugs in Combating SARS-CoV-2 DOI: http://dx.doi.org/10.5772/intechopen.99599*

formation of 3′-5′-phosphodiester bond in DNA chains thus preventing the replication of virus. An important aspect these drugs is that they inhibit the production of either negative or positive strands of DNA if incorporated during DNA- dependent DNA synthesis or RNA-dependent DNA synthesis [34].

Dose and Preparation: Didanosine: 400 Mg/Day (For >60 Kg Bw), 250 Mg/Day (< 50 Kg Bw); 1 Hour Before or 2 Hours After Meals; Dinex Ec, Dd Retro, Virosine Dr. 250, 400 Mg Tabs. Zidovudine (Azidothymidine, AZT): Adults 300 mg BD; Children 180 mg/m2 (max 200 mg) BD. Retrovir, Zidovir 100 Mg Cap 300 Mg Tab, 50 Mg/5 Ml Syr, Zidomax, Zydowin 100 Mg Cap, 300 Mg Tab (To Be Taken With Plenty Of Water).

Toxicity: Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD50 is 3084 mg/kg (orally in mice).

#### **7.2 Non-nucleoside reverse transcriptase inhibitor (NNRTIS)**

These are second class of reverse transcriptase inhibitors. They act by binding to reverse transcriptase and create hydrophobic pocket proximal to active site. This pocket generates novel spatial configuration of substrate binding site to decrease the overall activity of polymerase. By producing different configuration, synthesis of DNA slows down. NNRTIS are not effective against HIV-2 reverse transcriptase, because of non-competitive inhibitor action.

Dose and Preparation: Nevirapine: 200 mg/day oral to be increased after 2 weeks to 200 mg BD; Nevimune, Nevivir, Nevipan, Neviretro 200 Mg.

Toxicity: Symptoms of overdose include edema, erythema nodosum, fatigue, fever, headache, insomnia, nausea, pulmonary infiltrates, rash, vertigo, vomiting, and weight decrease. The most common adverse reaction is rash.

## **8. Protease inhbitor (PIs)**

The HIV viral proteinase enzyme which always fragment the replicative and structural proteins which evolve from major HIV genes mormally as gag and pol, is restrain by Ritonavir. Ritonavir inhibits the cleavage of gag-pol polyprotein leading in noninfectious immature viral particles. Ritonavir is also potent inhibitor of cytochrome P450 CYP3A4 isoenzyme which is present in both liver and small intestine. It is type II ligand which binds into CYP3A4 and further irreversibly to heme iron via thiazole nitrogen linkage which reduces proteins redox potential and impedes its reduction with cytochrome P450 reductase, redox partner. Ritonavir may edge cellular transport and efflux of other protease inhibitor via MRP efflux channel and P-glycoprotein.

Ritonavir/ Lopinavir is FDA approved therapy to treat HIV and is also reported to treat COVID19. However in patients with severe COVID-19, this combination showed no benefit [35].

PREPARATIONS: RITOVIR 250 mg tab, RITOMUNE, RITOMAX 100 mg cap.

Entry inhibitors obstruct HIV entry into CD4 cells in organism cells. They act in a different way other than nucleoside reverse transcriptase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors which function after they it has infected CD4 cells. They work by taking themselves to proteins which is composed of amino acids on superficial side of CD4 cells, the proteins present on surface of CD4 cells or on the surface of HIV. The proteins on HIV outer coat must bind to proteins present on the surface of CD4. Entry proteins inhibit the above process.

PREPARATION: - Efavirenz: is available as 600 mg tab, also FFERVEN, VIRANZ, and EVIRENZ, 200 mg cap, 600 mg tab.
