Frontiers in Anti-Infective Drug Discovery

The design of novel, safe, and effective drugs of natural origin is a challenging issue. To screen and uncover the infinite world of antimicrobial agents derived from secondary metabolites for drug discovery requires the integration of highthroughput technologies such as biology systems (bioinformatics) and omics technologies. These technologies include genomics, metagenomics, transcriptomes, proteomics, and metabolomics). In the present chapter, we focused on revisiting several aspects of these technologies in order to emphasize their unprecedented contribution to drug discovery. In addition, they represent a step forward in pharmacological and clinical research.

Despite the meritorious measures taken to curb the malaria scourge in the last two decades, the drug-resistance phenomenon threatens to reverse the gains made. Evidence of partial resistance against the first-line antimalarial drugs, the artemisinin-based combination therapies, in Africa, a region that accounts for 95% of global malaria cases, has aroused fears that it could spread fast and significantly jeopardise malaria control and eradication efforts. While the antimalarial drug discovery pipeline has several, encouraging candidates emerging through it, unfortunately, the attrition rate is high, with some candidates failing either in preclinical studies or clinical trials. Moreover, the rate of emergence of drug-resistant Plasmodium parasite strains far exceeds that of the drug discovery and development process. These challenges demand novel strategies to complement the discovery and development of new therapeutics. One such strategy is the reversal of Plasmodium falciparum resistance to old antimalarials by combining these drugs with agents that specifically target drug-resistance mechanisms. This strategy has been successfully used in the antibiotics field, with a classical successful example being the amoxicillin and clavulanic acid combination tion. In this chapter, we present a case for the need to discover and develop antimalarial drug-resistance reversal agents to prolong the efficacy and use of currently available antimalarial quinoline drugs as well as the re-use of old antimalarial quinoline drugs that have been rendered ineffective by drug-resistance. Furthermore, we provide an overview of noteworthy significant innovations that have been made in the field in search for antimalaria drug-resistance reversal agents. We conclude by providing perspectives on how these efforts can be expedited.

Although commonly used anti-infective vaccines in clinical practice are generally safe, certain local or systemic adverse reactions related to them may rarely occur. Actually, considering the general vaccination rates, the incidence of serious skin reactions (e.g . angioedema, anaphylaxis, Stevens–Johnson syndrome) is very low but vaccine-associated local cutaneous reactions such as erythema, edema, tenderness and pain at the injection sites are one of the most common complications of vaccines. Furthermore, a wide variety of specific or non-specific localized or generalized cutaneous adverse effects (e.g. lichenoid eruption, granuloma annulare, pseudolymphoma, erythema nodosum, erythema multiforme, Gianotti-Crosti syndrome, urticaria, lupus erythematosus, bullous pemphigoid, purpura) have been reported in the literature related with commonly used anti-infective vaccines. In this chapter, these adverse cutaneous reactions potentially associated with anti-infective vaccines were summarized with a comprehensive literature review.