Frontiers in Clinical Drug Research: Anti-Infectives

The development of multidrug-resistant bacteria (MDRB) and the emergence of new lethal diseases have raised the need for potent anti-infective agents with different killing action mechanisms that contribute to treating and/or supporting the currently used drugs. For this purpose, bacteriocins are considered excellent candidates with promising potential. Bacteriocins are ribosomally synthesized antimicrobial peptides that are produced by many bacterial genera. They are characterized by high thermal stability, being active over a wide pH range, and having specificity against selected bacterial strains by employing specific receptors on their cell membrane, which encourages bacteriocins to use in clinical applications as support and/or alternatives currently used antibiotics. Interestingly, bacteriocins have many advantages over antibiotics, such as the relative difficulty of developing resistance compared to broad-spectrum antibiotics. Moreover, due to their simple biosynthetic mechanisms, bacteriocins can be easily bioengineered, which improves their activity or specificity against selected microorganisms. Additionally, bacteriocins originating from lactic acid bacteria have the extra safety advantage because many LAB and their products are classified by the American Food and Drug Administration (FDA) to be generally recognized as safe (GRAS). Bacteriocins have promising pharmaceutical potentials as anti-infective agents, anti-MDRB agents, antileishmanial, and antiviral agents. Moreover, bacteriocins have been used to treat many ulcers, tumors, and cancers. In this chapter, we highlight the importance of bacteriocins as anti-infective agents, describing their common action mechanisms and recent clinical and therapeutical applications of bacteriocins. Finally, prospects in this field are discussed to discover and develop more diverse and efficient bacteriocins with potent anti-infective activities.

COVID-19 infection, caused by the SARS-CoV-2 virus, is associated with substantial morbidity and mortality. COVID-19 infection has three distinct phases: 1, early infection phase; 2, pulmonary phase; and 3, the hyperinflammatory phase. Despite a major focus on vaccines and new therapeutics, existing drugs sharing some known mechanistic with this virus, have also gained interest. The potential positioning of three mature innovative drugs, which could be of potential use in this pandemic environment, is discussed in this chapter: OM-85 and calcium dobesilate, and their salt form etamsylate, have revealed anti-viral and anti-inflammatory properties. OM-85, a bacterial extract originating from 21 pathogenic strains isolated from human lungs and indicated for the prevention of recurrent respiratory tract infections, stimulates both innate and adaptive immunity, resulting in non-specific loco-regional immune responses. It has shown anti-viral activity in a number of virus infection models, including influenza H1N1, rhinovirus, and more recently, coronaviruses. It has also shown some immunoregulatory properties. Accordingly, there is a rationale for further investigations on OM-85 to be used as prophylaxis for other respiratory infections and potentially in long-COVID. For calcium dobesilate, currently indicated for the treatment of microvascular diseases while preserving microvascular integrity via antioxidant and anti-inflammatory properties, there are cumulating data that could promote its potential use for the treatment during phase 2 to protect the vascular endothelium. Calcium dobesilate has anti-viral properties and was recently shown to interfere with the SARS-CoV-2 spike-protein binding to the ACE2 receptor. Accordingly, one could also postulate to use it during phase 1. Etamsylate, an anti-haemorrhagic and antiangiogenic agent that improves platelet adhesiveness and restores capillary resistance, is indicated for the prevention and treatment of capillary haemorrhages. Considering its mechanism of action, etamsylate could be envisage for use as potential treatment during phase 3 for viral-induced complications. Importantly, none of these afore mentioned drugs are currently approved for the prevention or treatment of SARS-CoV-2 viral infection. Further, the conduction of well-designed clinical trials is warranted.

The delicate balance between oxidants and antioxidants is a dynamic process, and when it hampers, oxidative stress occurs. Oxidative stress is now suggested to have a direct correlation with a viral infection, which in turn induces several oxidants like nitric oxide radicals, superoxide anions, hydroxyl radicals and their by-products (viz. hydrogen peroxide). All of these oxidants and their by-products contribute to viral pathogenesis and ultimately cause infectious diseases. The consequences of viral diseases account for considerable economic loss worldwide. In response to this, the scientific fraternity throughout the world is investigating the basic mechanisms underlying such diseases, as well as identifying novel therapeutic strategies for the prevention and treatment of such maladies. Over the last few decades, scientists oriented their research aims mostly towards elucidating the immunological basis of viral replication and pathogenesis, but a little is written about the implications of such research for drug development, which provides the impetus behind the creation of the present chapter enabling the readers to have a comprehensive overview on the involvement of free radicals in viral diseases along with latest updates towards developing novel therapeutic strategies against these diseases. The present chapter summarizes the relationship between oxidative stress, viral infection, and a variety of therapeutic strategies conferred by antioxidants. Antiviral therapeutic strategies based on antioxidants are considered to be a promising area of research against viral infections.