Antiviral Drugs For Respiratory Infections

Overview of Respiratory Infections

Respiratory tract infections are among clinical medicine's most common and important problems. Respiratory tract infections are infections of body parts involved in breathing, such as sinuses, lungs, throat and airways.¹ Respiratory infections, whether acute or chronic, are persistent in both adults and children, representing an increased economic burden on the healthcare system, mortality and morbidity.² The continuous emergence of new viruses, diverse strategies to survive and replicate, and the ability to resist antiviral drugs cause challenges to the existing antiviral drug therapy. For example, the novel coronavirus and drug resistance species of influenza virus prove that there is a need for new antiviral therapies.⁸

Importance of Antiviral Drugs in Managing Respiratory Infections

Antiviral drugs, such as coronaviruses or influenza viruses, are essential in managing respiratory infections. Antiviral drugs and vaccines are the two most effective measures to fight against viruses. However, the development of vaccines and antiviral agents is facing enormous challenges due to the constant variation of respiratory viruses and the prevalence of emerging and re-emerging viruses.³

The development of antiviral drugs has been a constant breakthrough in managing respiratory infections. Antiviral drugs inhibit the replication of viruses in the body, reducing the severity of the illness and the duration of the infection. Antiviral drugs are most effective when administered early in the course of illness.³

Types of Respiratory Infections

Upper-respiratory infections (URI)

Various bacteria and viruses can cause upper respiratory tract infections. These viruses cause various diseases in patients, including acute bronchitis, influenza and the common cold. Defining these patients' diseases is difficult due to the overlapping similarities in symptoms between other illnesses. 

Upper respiratory infections are self-limited irritations and swelling of the upper airways. 

Common colds continue to be the most common type of infection. The most common virus is the rhinovirus. Other viruses include influenza, adenovirus, and enterovirus.⁴

Risk factors for upper-respiratory tract infections (URI)

• Close contact with children: Both daycares and schools could increase the risk of URI
• Medical disorder: People with asthma and rhinitis are more likely to develop URI
• Smoking is a major contributing risk factor for URI
• Immunosuppressant individuals, including those with cystic fibrosis, HIV, and transplantation, are at high risk for URI
• Anatomical anomalies, such as  facial dysmorphic changes or polyposis, also increase the risk of URI⁴

Lower-respiratory infection (LRI)

Infections of the lower respiratory tract are mostly bronchitis, bronchiolitis, and pneumonia. These diseases, such as pneumonia, can be fatal. Although viruses and fungi can all cause lower respiratory tract infections, bacteria are the dominant pathogens, accounting for a much higher percentage of lower than upper respiratory tract infections.⁵

A variety of bacteria and viruses usually cause lower respiratory tract infections. LRI is a contagious infection, which means it can easily be spread from one person to another through close contact. LRI generally last from one week to three weeks. However, if LRI lasts more than 21 days, it could indicate a severe LRI.⁶

Types of lower-respiratory infections

There are various types of LRI, depending on the type of virus and bacteria that cause them. Many of them are treatable. However, if they remain untreated, they can cause serious healthcare complications. 

Important types of LRI are the following:

• Pneumonia: is a lower respiratory infection in which the air sacs in the lungs are filled with pus or fluid. This condition causes swelling in the lungs. Infants and people with weakened immune systems are more prone to developing pneumonia. 
• Bronchitis: This is the swelling in the lining of the bronchial tube, mainly the large airways. Bronchitis is more common in older adults and infants under.⁵ 
• Bronchiolitis: It refers to inflammation of the small airways. It is more common in infants and toddlers under the age of 2. 
• Tuberculosis: It is an infectious disease that affects the lungs. Tuberculosis can happen to people of any age. 

Lower respiratory infection is highly infectious, and there are a variety of factors that, if taken into action, can prevent the spread of infection, such as washing hands and covering the mouth when sneezing. Getting vaccines and avoiding touching objects are some of the ways you can limit the spread of infection.⁶

Understanding Antiviral Drugs

Antiviral drugs are a class of medicines that are used for the treatment of infections. Drugs that combat viral infections are called antiviral drugs. Viruses are among the significant pathogenic agents that cause many severe diseases in humans, animals and plants.⁷

Specific antiviral drugs are used for treating particular pathogens, just like antibiotics for bacteria. Unlike most antibiotics, antiviral drugs do not destroy their target pathogens but inhibit their development. 

As the viruses use their host cells to replicate, it is challenging to design a safe and effective antiviral drug. Therefore, finding drug targets that interfere with viruses without damaging the host cells is hard. Furthermore, significant complications in developing antiviral drugs and vaccines are because of their viral variations. One of the essential ways of finding antiviral drugs is computer-based drug discovery. For this approach, nelfinavir is an example discovered in the 1990s for the treatment of immunodeficiency virus (HIV) infection.⁸

The most commonly used antiviral drugs include:

• Neuraminidase inhibitors: These drugs block the activity of neuraminidase enzymes, which are essential for releasing new virus particles from infected cells. The most commonly used neuraminidase inhibitors are oseltamivir phosphate, also called Tamiflu , Zanamivir and peramivir. 
• Protease inhibitors: These drugs inhibit the activity of protease enzymes, which are essential for the replication of viruses. Examples of such inhibitors include remdesivir.
• Fusion inhibitors: These drugs work by blocking the fusion of the virus with the host cell membranes, preventing the virus from entering the host cells. For example, enfuvirtide is also called Fuzeon.
• Entry inhibitors: These drugs block the entry of the virus into the host cells. Entry inhibitors include maraviroc.^9,10

Development and Challenges

Despite modern tools and stringent measures for quality control, only a few antiviral drugs are getting approved for human use either due to the side effects or resistance of antiviral medications, with an increase in the awareness about the viruses, their mechanisms of action and the rapid development of novel strategies and techniques for antiviral drugs development. The current scenario worldwide indicates the continuous emergence of microbial threats at an accelerating pace, mainly due to unprecedented climate change and globalisation.⁷

Role of Antiviral Drugs in Pandemics

Respiratory viral infections are a significant cause of the highly mortal pandemic. They are impacting socio-economic development and the healthcare system globally. These emerging deadly viruses develop new survival strategies to live inside host cells and trick the host's immune system. 

Currently, medical facilities, therapies and research development teams of every country kneel before the novel coronavirus, which has claimed nearly 3 million lives to date. Thus, there is an urgent requirement for novel treatment strategies to combat these emerging respiratory infections.⁸

Future Directions and Innovations

In recent years, there has been tremendous progress in understanding diseases' genetic basis and molecular mechanisms. Various new drugs have been formulated, and more development is underway. 

New infectious diseases such as COVID-19 remain a challenge. Drug failure in human trials is a general process that needs to be addressed and challenged. A better understanding of viruses will make it possible to establish valuable measures for fighting against viral diseases, and researchers worldwide are putting their efforts into controlling the spread of viral infection.⁸

FAQs

How do you avoid passing respiratory infections to others?

• Always cover your mouth when sneezing or coughing
• Washing hands can limit the spread of an infection 
• Always use new tissue when sneezing or coughing: throw away used tissues¹ 

How to avoid getting a respiratory infection?

If you are at high risk of getting infections, such as if you are over the age of 65 or suffer from long-term health conditions, you should:

• Consult with your GP and ask for the flu vaccination, 
• Ask if you should have pneumococcal vaccine - to prevent you from getting pneumonia
• Stop smoking if you smoke 
• Avoid drinking alcohol altogether¹

Summary

Respiratory infections represent the world’s third and most common cause of infection. Incidence is underestimated because the infections are mild and not anticipated. 

Antiviral drugs play a crucial role in managing respiratory infections caused by viruses. They effectively reduce the severity of the symptoms and the duration of illnesses. Vaccines and antiviral drugs face challenges due to the constantly changing nature of the virus. Therefore, finding new methods for designing and developing new antiviral drugs is essential.