MmpL3 Inhibition as a Promising Approach to Develop Novel Therapies against Tuberculosis: A Spotlight on SQ109, Clinical Studies, and Patents Literature

Tuberculosis (TB) is accountable for considerable global morbidity and mortality. Effective TB therapy with multiple drugs completes in about six months. The longer duration of TB therapy challenges patient compliance and contributes to treatment collapse and drug resistance (DR) progress. Therefore, new medications with an innovative mechanism of action are desperately required to shorten the TB therapy’s duration and effective TB control. The mycobacterial membrane protein Large 3 (MmpL3) is a novel, mycobacteria-conserved and recognized promiscuous drug target used in the development of better treatments for multi-drug resistance TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). This article spotlights MmpL3, the clinical studies of its inhibitor (SQ109), and the patent literature. The literature on MmpL3 inhibitors was searched on PubMed and freely available patent databases (Espacenet, USPTO, and PatentScope). SQ109, an analog of ethambutol (EMB), is an established MmpL3 inhibitor and has completed Phase 2b-3 clinical trials. Infectex and Sequella are developing orally active SQ109 in partnership to treat MDR pulmonary TB. SQ109 has demonstrated activity against drug-sensitive (DS) and drug-resistant (DR) Mycobacterium tuberculosis (Mtb) and a synergistic effect with isoniazid (INH), rifampicin (RIF), clofazimine (CFZ), and bedaquiline (BNQ). The combination of SQ109, clofazimine, bedaquiline, and pyrazinamide (PZA) has been patented due to its excellent anti-TB activity against MDR-TB, XDR-TB, and latent-TB. The combinations of SQ109 with other anti-TB drugs (chloroquine, hydroxychloroquine, and sutezolid) have also been claimed in the patent literature. SQ109 is more potent than EMB and could substitute EMB in the intensive stage of TB treatment with the three- or four-drug combination. Developing MmpL3 inhibitors is a promising approach to fighting the challenges associated with DS-TB and DR-TB. The authors foresee MmpL3 inhibitors such as SQ109 as future drugs for TB treatment

PREVALENCE OF SICKLE-CELL DISEASE IN SAUDI ARABIA: A SYSTEMATIC REVIEW

Background: A series of hemoglobinopathies known collectively as sickle cell disease (SCD) contain abnormalities in the gene encoding the beta component of haemoglobin. There are other subcategories that fall under the SCD umbrella, including sickle cell disease (SCD), haemoglobin SC disease (HbSC), and haemoglobin sickle-beta thalassemia (beta-thalassemia positive or beta-thalassemia negative). The prevalence of SCD varies greatly across Saudi Arabia, with the Eastern province having the greatest frequency and the southern regions having the second-highest prevalence. The reported sickle-cell prevalence ranges from 2% to 27%, and in some regions, up to 2.6% of people will have SCD. Objectives: The study aims to summarize current evidences regarding Prevalence of Sickle-Cell Disease in Saudi Arabia. Methods: For article selection, the PubMed database and EBSCO Information Services were used. All relevant articles relevant with our topic and other articles were used in our review. Other articles that were not related to this field were excluded. The data was extracted in a specific format that was reviewed by the group members. Conclusion: Although the prevenance of sickle cell anemia is relatively high due to multiple reasons such as consanguinity, the prevalence of genetic diseases in Saudi Arabia may be significantly lowered during the following decades as a result of premarital screening there. Also, acute chest syndrome in SCD patients is relatively infrequent in Saudi Arabia's Eastern Province, it nonetheless has a major impact on morbidity and death. If patients with African haplotypes are compared, it has a low prevalence and recurrence