Inhaled aprotinin found to reduce viral load in mild to moderate COVID-19

Much research has been done to control or mitigate the social and economic impact of the 2019 coronavirus disease (COVID-19) pandemic.

As new variants of the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to emerge, the ‘new normal’ appears to be a scenario in which humans coexist with the virus.

However, many people are at increased risk of severe COVID-19 due to comorbidities such as obesity, hypertension, type 2 diabetes, aging and falling socioeconomic status. Antiviral drugs must be developed to combat this threat.

A recent paper describes the use of aprotinin, a protease inhibitor that acts across several pathways, to reduce the severity of the condition.

prologue

Several drugs are approved for use in COVID-19, including molnupiravir, paxlovid (nilmatrelvir/ritonavir combination), and lopinavir/ritonavir. However, they interact with other drugs, are relatively expensive, and have significant side effects. Furthermore, it may not help once COVID-19-related inflammation sets in or help prevent COVID-19.

In light of these limitations, aprotinin has been investigated for its potential utility as an antiviral agent. Inhibitor. spike proteinIt is essential for spike recognition by the host cell surface angiotensin-converting enzyme 2 (ACE2) receptor, which mediates viral attachment and entry.

The authors of the current study conducted a phase III trial called TAC (Aprotinin Treatment for COVID-19). demonstrate safety, effectiveness of Nebulized aprotinin in moderate COVID-19 led to improved clinical outcomes using inhaled aprotinin in moderate COVID-19 patients hospitalized with pneumonia. These patients required less supplemental oxygen and had a shorter duration of treatment than the control group who received placebo.

Aprotinin is convenient for use in the clinical setting, has potential for COVID-19 prophylaxis, and is useful in mild outpatient settings, making it suitable for use in low-resource settings. Nebulization avoids systemic administration and thus reduces the risk of side effects.

As people socially mingle or move back into other environments, secondary infections and the possibility of co-infection with other pathogens, such as seasonal influenza, can lead to more severe infections. Even in this hypothetical setting, aprotinin is an interesting drug due to its ability to act against a wide range of viruses.

In previous studies, researchers were unable to measure. viral load in all patients. Current research European Journal of Clinical Research, undertook to measure viral load reduction in archived tracheobronchial samples from a group of moderately ill COVID-19 patients. This demonstrates its ability to prevent disease progression and treat severe cases.

findings

Researchers used reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to measure viral load in a group of moderate COVID-19 patients. Two measurements were obtained. one at baseline and one after his 5 days of standard her COVID-19 management with aprotinin treatment. This group included her 28 patients, while a control group of 32 patients was given standard care only.

The study involved four medical centers in Spain, and all patients tested positive for the virus within 48 hours of being randomized to treatment or control groups. I had pneumonia.

Although PCR results were similar between groups at baseline, the viral load was significantly reduced in the aprotinin-treated group. In addition, the aprotinin group had shorter treatment durations overall, 5.5 days and he 7.4 days, respectively.

The aprotinin group had a more significant reduction in viral load of -2.8 log copies/mL compared to only -0.8 in the control group. Platelet and D-dimer levels were 1.5-fold and more than 7-fold lower in the aprotinin group compared with controls. On the other hand, fibrinogen levels decreased equally in both groups.

These results were independent of age, gender, or body mass index (BMI).

implication

The current study showed a reduction in viral load with aprotinin inhalation in patients with moderate COVID-19. Previous studies have shown that inhaled aprotinin and its intravenous use in combination with favipiravir are useful in such patients. The combination resulted in lower viral loads, fewer intensive care unit admissions, shorter hospital stays, and improved lung injury markers by day 14 of treatment. Activity was attributed to favipiravir, and aprotinin was thought to provide clinical improvement.

Aprotinin is superior to camostat mesylate, an inhibitor of the host protease TMPRSS2, in reducing SARS-CoV-2 entry into target cells in vitroThis is because the former has a wider range of activity and can effectively target viruses.

Aprotinin prevents thrombosis and inflammation through its effects on host proteases and coagulation regulators such as kallikrein that are activated by the SARS-CoV-2 capsid protein. The former prevents SARS-CoV-2 activation and cell entry and replication within host cells.

Kallikrein activation causes neutrophilia with extracellular trapping of neutrophils (NETosis) and causes microthrombosis. In addition to kallikrein inhibition, aprotinin inhibits inflammatory mediators, reduces leukocyte adhesion molecule expression, reduces tracheobronchial secretion, and prevents complement activation.

Our findings may reflect an aprotinin-mediated immunomodulatory/anti-inflammatory effect, secondary to a reduction in viral load, involved in rapid hospital discharge in patients receiving aprotinin + standard of care. and may shorten treatment“

Therefore, aprotinin is a potential antiviral agent for COVID-19 and further studies are shown to demonstrate its ability to prevent infection or modulate disease severity in this condition.