A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection.

Antiviral therapies are integral in the fight against SARS-CoV-2 (i.e. severe acute respiratory syndrome coronavirus 2), the causative agent of COVID-19. Antiviral therapeutics can be divided into categories based on how they combat the virus, including viral entry into the host cell, viral replication, protein trafficking, post-translational processing, and immune response regulation. Drugs that target how the virus enters the cell include: Evusheld, REGEN-COV, bamlanivimab and etesevimab, bebtelovimab, sotrovimab, Arbidol, nitazoxanide, and chloroquine. Drugs that prevent the virus from replicating include: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, and Kaletra. Drugs that interfere with protein trafficking and post-translational processing include nitazoxanide and ivermectin. Lastly, drugs that target immune response regulation include interferons and the use of anti-inflammatory drugs such as dexamethasone. Antiviral therapies offer an alternative solution for those unable or unwilling to be vaccinated and are a vital weapon in the battle against the global pandemic. Learning more about these therapies helps raise awareness in the general population about the options available to them with respect to aiding in the reduction of the severity of COVID-19 infection. In this 'A Guide To' article, we provide an in-depth insight into the development of antiviral therapeutics against SARS-CoV-2 and their ability to help fight COVID-19.

[Effects of treatment with ACE and serotonin inhibitors on arterial blood pressure at rest and cycloergometric exercise and on systolic time intervals: comparison of enalapril and ketanserin]. / Effetto della terapia con ACE inibitori ed inibitori della serotonina sulla pressione arteriosa a riposo, sotto sforzo cicloergometrico e sugli intervalli di tempi sistolici: confronto tra enalapril e ketanserina.

Exercise tolerance test gives important diagnostic, prognostic and therapeutic information in hypertensive patients. One hundred essential hypertensive patients were treated with enalapril: 10 mg/day, ketanserin: 40 mg/day and associated enalapril: 5mg/day + ketanserin: 20 mg/day for three different periods of three months for each one, with a wash-out period of 15 days after each therapeutic cycle. We used ACE and ketanserin because they have a hypotensive effect without developing tolerance, metabolic effects, rebound events in case of sudden interruption. These pharmacologic agents, which are active by themselves, can also be used in association with other hypotensive agents. Two exercise tolerance tests were carried out on each patient before and after each therapeutic period. Clinostatic systolic time intervals were assessed before and after treatment. Enalapril and ketanserin reduced systolic and diastolic pressure in basal condition and after exercise tolerance test, without any interference on heart rate. The association of the two hypotensive agents resulted more active, even with a halved dose. The improving of the double product and the systolic time intervals confirm the efficacy of these treatments. Side effects were mild.

Alterations of systolic time intervals in the assessment of myocardial function during hypertensive pregnancy.

The alterations in the systolic time intervals caused by hypertension during pregnancy have been investigated. A group of 20 women who developed hypertension only during pregnancy (HP), and a group of 16 women who began pregnancy with established hypertension (EHP) were matched with 25 normal pregnant women (N). the study was performed (1) during the third trimester, (2) five days after delivery and (3) five weeks after delivery, both in supine and in lateral postures. In the third trimester the two hypertensive groups, when compared with the normal group, were characterized by a shorter left ventricular ejection time (LVETi: 407 +/- 3 ms for the normal group v. 390 +/- 2 ms for the HPO group, P less than 0.001; v. 398 +/- 2 ms for the EHP group, P less than 0.02), and a longer pre-ejection period (PEPi: 138 +/- 2 ms for the normal group v. 154 +/- 2 ms for the HP group P less than 0.001; v. 145 +/- 1 ms for the EHP group, P less than 0.05). When the two hypertensive groups were compared with each other the HP group showed a shortened LVET and a prolonged PEP (P less than 0.01), and also a slower heart rate (HP 74 +/- 3 b min-1. EHP 83 +/- 3 b min-1 P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Reversible alteration of myocardial function in gestational diabetes.

Left ventricular function was evaluated in 24 women who developed impaired glucose tolerance only during their pregnancy, i.e. patients with gestational diabetes. The results were compared with those of 25 normal pregnant women and with those of 17 pregnant women with clinical diabetes. The method of systolic time intervals was applied. At the third trimester of pregnancy, both the women with overt diabetes and those with gestational diabetes, when compared with normal pregnant subjects, had a more prolonged pre-ejection period (PEP) and a shorter left ventricular ejection time (LVET) and, consequently, a higher PEP/LVET ratio. Five weeks after delivery, abnormalities of systolic time intervals persisted in patients with clinical diabetes, but there were no differences at this time between patients with gestational diabetes and those in the control group. It is concluded that when a cardiac load is superimposed on patients who develop diabetes only under conditions of stress, as in pregnancy (gestational diabetes), abnormalities of myocardial function appear, which revert to normal when the stressful event is removed.

[Cardiac valvular disease and pregnancy. Haemodynamic aspects and importance of decubitus]. / Cardiopatie valvolari e gravidanza. Aspetti emodinamici ed importanza del decubito.

During the 3rd trimester of pregnancy, 26 women with aortic or mitral valve disease (II class NYHA) have undergone bedside right heart catheterization. Total pulmonary resistances (RPT) have been studied in supine (DS) and lateral (DL) decubitus. The results are compared with those of 7 normal women. It is known that the change from the supine to the lateral posture increases venous return (and cardiac output) by removing the compression which the pregnant uterus causes to the inferior vena cava. This is achieved without increasing the mean pulmonary pressure (PPM) and total pulmonary resistances (RPT); women with mitral and aortic stenosis have little or no increase of cardiac output but always a marked increase of PPM and RPT; the response in patients with aortic and mitral incompetence is closer to normal; an intermediate response was observed in patients with a mitral stenosis and insufficiency. The valvular heart diseases with stenosis badly tolerate the increased cardiovascular burden of pregnancy and are unable to accommodate the increased venous return induced by postural changes, which induces marked elevation of pulmonary pressure and resistances.

[Systolic times adjustment during pregnancy and puerperium (author's transl)]. / Modificazione dei tempi sistolici durante la gravidanza e il puerperio.

During pregnancy and the post partum period important cardiovascular adjustments take place, which for ethical views need a non invasive approach. In the present work we studied the alterations of the Systolic Time Intervals in both supine and lateral decubitus during each trimester and at the fifth day and fifth week after delivery. In the first part of pregnancy a significant reduction of the preejection time (PE) and PE/EVS with an increase of the left ventricular ejection time (EVS) become evident. In the second part the picture reverses to a significantly reduced EVS and increased PE and PE/EVS. This picture even if decreasing, is present in the post partum period. The first part of pregnancy is characterized by a hyperkinetic condition; in the second one the position of the woman becomes important, and the reduction of the EVS is at least partially due to an impaired venous return (compression of the vena cava by the gravid uterus). The persistence of altered systolic time intervals in the post partum (increased PE/EVS) suggest an impaired myocardial performance.

[Preliminary data on the pharmacokinetics of digoxin in pregnancy]. / Dati preliminari sulla farmacocinetica della digossina in gravidanza.

The pharmacokinetics of digoxin were investigated in 8 pregnant women (2-3 months before delivery), in three women 3 months after delivery, and in 3 non-pregnant women, after i.v. injection of 500 microgram. Digoxin was evaluated in serum with the radioimmunoassay method. In pregnant women C1 (concentration of digoxin in the first compartment) and V1 (volume of the first compartment) were higher and C2, K1-2, K2-1 (exchange constants) and Kel (elimination constant) were all lower than the values obtained in both post-partum and non-pregnant women. Our data lead us to think that the exchange (both uptake and release) between the first and second compartment is lowered in pregnancy.