Amphiphilic Heparinoids as Potent Antiviral Agents against SARS-CoV-2.

Herein, we report the synthesis and biological evaluation of a novel series of heparinoid amphiphiles as inhibitors of heparanase and SARS-CoV-2. By employing a tailor-made synthetic strategy, a library of highly sulfated homo-oligosaccharides bearing d-glucose or a C5-epimer (i.e., l-idose or l-iduronic acid) conjugated with various lipophilic groups was synthesized and investigated for antiviral activity. Sulfated higher oligosaccharides of d-glucose or l-idose with lipophilic aglycones displayed potent anti-SARS-CoV-2 and antiheparanse activity, similar to or better than pixatimod (PG545), and were more potent than their isosteric l-iduronic acid congeners. Lipophilic groups such as cholestanol and C18-aliphatic substitution are more advantageous than functional group appended lipophilic moieties. These findings confirm that fine-tuning of higher oligosaccharides, degree of sulfation, and lipophilic groups can yield compounds with potent anti-SARS-CoV-2 activity.

Alterations in retrobulbar haemodynamics in thyroid eye disease.

PURPOSE: To study the orbital perfusion parameters of ophthalmic artery (OA) and central retinal artery (CRA) in inactive TED and the changes following surgical decompression. METHODS: Non-randomised clinical trial. 24 inactive moderate-to-severe TED orbits of 24 euthyroid cases underwent surgical decompression and examined again at 3 months. The peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistivity index (RI) of OA and CRA were evaluated using colour doppler imaging and normative database was established using 18 healthy controls. RESULTS: The mean age was 39.38 ± 12.56 years and male: female ratio was 1: 1.18. Intraocular pressure was higher, and CRA-PSV, CRA-RI, OA-PSV, and OA-EDV were lower in TED in comparison to heathy orbits. The CRA-PSV, CRA-EDV, OA-PSV, and OA-EDV negatively correlated with proptosis and duration of thyroid disease. The area under curve of OA-PSV (95% CI:0.964-1.000, p < 0.001) and OA-EDV (95% CI:0.699-0.905, p < 0.001) helped in differentiating TED orbits from HC, and in predicting the severity of disease. Post decompression, CRA-PSV, CRA-EDV, OA-PSV, and OA-EDV improved, with decrease in CRA-RI and OA-RI in both lipogenic and MO. CONCLUSIONS: The orbital perfusion is reduced in inactive TED. The changes in OA flow velocities can help in differentiating inactive TED from healthy orbits and progression of TED. Sequential orbital CDI of OA and CRA can serve as an objective tool for case selection and monitoring response to surgical decompression.

SARS-CoV-2 triggers complement activation through interactions with heparan sulfate.

Objectives: To determine whether SARS-CoV-2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant effect. Methods: SARS-CoV-2 was inoculated into a human lepirudin-anticoagulated whole blood model, which contains a full repertoire of complement factors and leukocytes that express complement receptors. Complement activation was determined by measuring C5a production with an ELISA, and pretreatment with specific inhibitors was used to identify the pathways involved. The functional significance of this was then assessed by measuring markers of C5a signalling including leukocyte C5aR1 internalisation and CD11b upregulation with flow cytometry. Results: SARS-CoV-2 inoculation in this whole blood model caused progressive C5a production over 24 h, which was significantly reduced by inhibitors for factor B, C3, C5 and heparan sulfate. However, this phenomenon could not be replicated in cell-free plasma, highlighting the requirement for cell surface interactions with heparan sulfate. Functional analysis of this phenomenon revealed that C5aR1 signalling and CD11b upregulation in granulocytes and monocytes was delayed and only occurred after 24 h. Conclusion: SARS-CoV-2 is a noncanonical alternative pathway activator that progressively triggers complement activation through interactions with heparan sulfate.

Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction.

Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.

Ocular sequelae in severe COVID-19 recovered patients of second wave.

Purpose: To evaluate the retinal microvascular changes in patients, recovered from severe COVID-19 during the second wave of the pandemic in North India. Methods: In this observational cross-sectional study, 70 eyes of 35 patients who recovered from severe COVID-19 during the second wave underwent detailed ophthalmic evaluation 4-6 weeks after discharge. Twelve controls were also enrolled, and the difference in the findings between the case and control groups on optical coherence tomography (OCTA) were studied. Result: The ages of study participants ranged from 27 to 60 years with the male:female ratio being 1.05:1. The fundus changes suggestive of ischemia in the form of cotton wool spots and vascular tortuosity were seen in 25 eyes (35.71%). Increased venous tortuosity was the most common finding seen in 23 eyes (32.85%), of which 10 eyes (28.57%) had concurrent hypertensive retinopathy (HTR) changes. There was a significant reduction in the mean vascular density (VD) and perfusion density (PD) for both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at inner, outer ring, and whole (P < 0.05). Foveal avascular zone was significantly enlarged in both the SCP (P = 0.01) and the DCP (P = 0.03). The mean ganglion cell-inner plexiform layer (GC-IPL) was significantly reduced in comparison to controls (P < 0.001). Conclusion: Severe COVID-19 can result in microvascular changes at the macula in the form of reduction in vascular and perfusion density, which can be evaluated using OCTA. As structural changes precede functional changes, a close watch is recommended in patients showing compromise in retinal microvasculature.

Structural Insights into Pixatimod (PG545) Inhibition of Heparanase, a Key Enzyme in Cancer and Viral Infections.

Pixatimod (PG545), a heparan sulfate (HS) mimetic and anticancer agent currently in clinical trials, is a potent inhibitor of heparanase. Heparanase is an endo-ß-glucuronidase that degrades HS in the extracellular matrix and basement membranes and is implicated in numerous pathological processes such as cancer and viral infections, including SARS-CoV-2. To understand how PG545 interacts with heparanase, we firstly carried out a conformational analysis through a combination of NMR experiments and molecular modelling which showed that the reducing end ß-D-glucose residue of PG545 adopts a distorted conformation. This was followed by docking and molecular dynamics simulations to study the interactions of PG545 with heparanase, revealing that PG545 is able to block the active site by binding in different conformations, with the cholestanol side-chain making important hydrophobic interactions. While PG545 blocks its natural substrate HS from binding to the active site, small synthetic heparanase substrates are only partially excluded, and thus pentasaccharide or larger substrates are preferred for assaying this class of inhibitor. This study provides new insights for the design of next-generation heparanase inhibitors and substrates.

Clinico-Radiological-Pathological Correlation of Visual Loss in COVID-Associated Rhino-Orbito-Cerebral Mucormycosis.

PURPOSE: To correlate the clinical, radiological, and histopathological features in Covid-associated Rhino-orbito-cerebral mucormycosis cases presenting with acute visual loss. DESIGN: Cross-sectional study. METHODS: Covid-associated Rhino-orbito-cerebral mucormycosis cases with unilateral visual loss, planned for exenteration, underwent orbital and ophthalmological ocular examination. The available radiological sequences, doppler ultrasonography and histopathology findings were correlated with clinical manifestations. RESULTS: The median age was 51 years and the male: female ratio was 3:1. All except one presented with unilateral ophthalmoplegia. The ocular media were hazy in 2 eyes. In 8 eyes, retinal changes were suggestive of occlusion of CRA (6), combined occlusion of CRA and central retinal vein (1), and myopic degeneration with hypertensive retinopathy (1). The contralateral eye showed retinal ischemic changes in one patient. Radiological imaging showed orbital apex involvement in the 10 affected eyes and one contralateral eye. Ipsilateral cavernous sinus thrombosis, diffusion restriction on MRI of optic nerve, internal carotid artery narrowing/thrombosis, and cortical watershed infarcts were seen in 8, 4, 4, and 2 cases, respectively. The blood flow in CRA and ophthalmic artery was absent or reduced in all the 10 affected eyes and in 1 contralateral eye. On histopathology, orbital fat necrosis, fungal hyphae, acute inflammation, granuloma formation, ischemic thrombosis of ophthalmic artery was observed in 10 specimens. CRA was patent in 9 and thrombosed in 1 eye. Optic nerve was ischemic in 8 and viable in 2 eyes. CONCLUSION: Acute visual loss in ROCM cases is associated with orbital apex involvement and thrombotic ischemia of ophthalmic artery. Cessation of flow in CRA possibly occurs secondary to ophthalmic artery thrombosis.

Development of Improved Synthetic Routes to Pixatimod (PG545), a Sulfated Oligosaccharide-Steroid Conjugate.

The heparan sulfate (HS) mimetic pixatimod (PG545) is a highly potent inhibitor of angiogenesis, tumor growth, and metastasis currently in clinical trials for cancer. PG545 has also demonstrated potent antiviral activity against numerous HS-dependent viruses, including SARS-CoV-2, and shows promise as an antiviral drug for the treatment of COVID-19. Structurally, PG545 consists of a fully sulfated tetrasaccharide conjugated to the steroid 5α-cholestan-3ß-ol. The reported synthesis of PG545 suffers from a low yield and poor selectivity in the critical glycosylation step. Given its clinical importance, new efficient routes for the synthesis of PG545 and analogues were developed. Particular attention was given to improving the key glycosylation step by using more stable protecting groups and optimized glycosyl donors.

Rhino-Orbito-Cerebral-Mucormycosis During the COVID-19 Second Wave in 2021 - A Preliminary Report from a Single Hospital.

PURPOSE: To list the clinico-epidemiological profile and possible risk factors of COVID-19 associated rhino-orbital-cerebral mucormycosis (CA-ROCM) patients presenting to a COVID dedicated hospital during the second wave of COVID-19 in India. PATIENTS AND METHODS: A cross-sectional, single-center study was done on 60 cases of probable CA-ROCM based on clinical features and supportive diagnostic nasal endoscopic findings and/or radiologic findings. Patients with recent or active COVID-19 were included. The demographic profile, clinical features, possible risk factors and diagnostic workup (microbiological, pathological and radiological) were analysed to identify the triggering factors for CA-ROCM. RESULTS: The age of patients ranged from 29 to 75 years and male-female ratio was 3:1. The duration between the first positive COVID report and onset of CA-ROCM was 0 to 47 days. Forty-nine (81.66%) patients had a recent COVID infection and 11 (18.33%) had active COVID infection at presentation. Thirty-five patients (58%) had ocular/orbital involvement at presentation. In the affected eye, 10 had no perception of light and in the rest visual acuity ranged from log MAR 0 to +1.5. Ocular manifestations were ptosis (29), ophthalmoplegia (23), periocular tenderness and edema (33), proptosis (14), black discoloration of eyelids (3), facial palsy (3), endophthalmitis (4), retinal artery occlusion (8), disc edema (4) and disc pallor (5). Twenty-two (25%) patients had neither received steroids nor oxygen. Thirty patients (50%) were managed with oxygen while 38 patients (63.3%) with systemic steroids. The most common risk factor was diabetes in 59 patients. The average glycosylated hemoglobin (HbA1c) was 10.31 ± 2.59%. Systemic Amphotericin B was started in all the patients. Radical surgical debridement was performed in 12 patients and the remaining were planned. CONCLUSION: SARS-CoV-2 variant with accompanying glycaemic dysregulation was found to be the triggering factor for the epidemic of CA-ROCM.

From Cancer to COVID-19: A Perspective on Targeting Heparan Sulfate-Protein Interactions.

Heparan sulfate (HS) is a complex, polyanionic polysaccharide ubiquitously expressed on cell surfaces and in the extracellular matrix. HS interacts with numerous proteins to mediate a vast array of biological and pathological processes. Inhibition of HS-protein interactions is thus an attractive approach for new therapeutic development for cancer and infectious diseases, including COVID-19; however, synthesis of well-defined native HS oligosaccharides remains challenging. This has aroused significant interest in the development of HS mimetics which are more synthetically tractable and have fewer side effects, such as undesired anticoagulant activity. This account provides a perspective on the design and synthesis of different classes of HS mimetics with useful properties, and the development of various assays and molecular modelling tools to progress our understanding of their interactions with HS-binding proteins.

Comparative Evaluation of Tears and Nasopharyngeal Swab for SARS-CoV-2 in COVID-19 Dedicated Intensive Care Unit Patients.

Purpose: To compare the cycle threshold (Ct) values of tears and nasopharyngeal (NP) swab in severe COVID-19 ICU patients with positive NP swabs.Procedure: A cross-sectional study for the detection of SARS-CoV-2 by real-time RT-PCR on simultaneously collected NP swabs and tears was performed. Detailed demographic profile, including comorbidities, ocular, and systemic features were analyzed.Results: In the 78 cases, the mean tear positivity was 26.92% (21/78), 2 tear samples being positive despite a negative NP swab. The mean Ct value of tears and NP were 28.17 ± 4.76 and 23.71 ± 6.19, respectively (p= .003). None of the cases had ocular findings or relationship between tear positivity and comorbidity.Conclusions: The viral load of tears is less than the NP secretions with the possibility of prolonged shedding in tears. Tears act as an additional source of contact transmission in ICU that can possibly be decreased by frequent hand hygiene by the patient.Abbreviations: SARS-CoV-2: Severe acute respiratory syndrome coronavirus; RT-PCR: Real-time Reverse transcriptase-polymerase chain reaction; COVID-19: Corona virus disease 2019; ICU: Intensive care unit; RdRp: RNA-dependent RNA polymerase; ORF 1b: Open reading frame 1b; AIIR: Airborne infection isolation room; HCW: Health care workers; VTM: viral transport media; NP: Nasopharyngeal swab; PPE: Personal protective equipment.

Role of intrastromal vancomycin in recalcitrant corneal abscess after phacoemulsification.

Side port infection and corneal abscess after cataract surgery can produce devastating outcomes. Topical antibacterial drugs are the mainstay in management of these cases. Although intrastromal antifungal agents are an established modality for fungal keratitis, such use of antibacterial agents is rarely reported due to better pharmacokinetic profile of antibacterial agents.We report a case of methicillin-resistant Staphylococcus aureus corneal abscess following phacoemulsification that responded to intrastromal vancomycin injection in addition to conventional therapy.This case of postphacoemulsification corneal abscess highlights the importance of postoperative hygiene practices, use of anterior segment optical coherence tomography for monitoring these patients and use of intrastromal vancomycin as an adjunct to topical and systemic therapy.

Clinical Presentation and Management Strategies in Intraorbital Foreign Bodies.

The authors present a retrospective, observational case study of seven patients, who presented with retained Intra-Orbital Foreign Bodies (IOrbFBs) following penetrating orbital injury at a tertiary eye hospital over a period of one year. Cases were reviewed for epidemiological features, mechanism of injury, nature of foreign body, clinical features, imaging modality, associated complications, management outcomes, and the final prognosis. The mean age of presentation was 27.43 years. Amongst the seven patients, two were children (aged <10 years). The male : female ratio was 4 : 3. Of the seven retained IOrbFBs, two were plastic, two wooden, and three metallic in nature (one gunshot injury, one ball projectile (commonly referred to as BB) injury, and one with knife). Two out of seven had no light perception at presentation. The periocular location of the foreign bodies was inferior in 4 cases and medial in 3 cases. Computed Tomography scan confirmed the diagnosis in five cases and Magnetic Resonance Imaging (MRI) was diagnostic in one. Surgical intervention was done in five cases, and two cases were managed conservatively. The authors conclude that favourable outcome can be achieved even without surgical removal in cases of inert metallic/inorganic IOrbFBs. The properties of plastic FBs can frequently render them invisible on imaging, or they may mimic chronic inflammatory conditions like tuberculosis. Long-standing wooden IOrbFBs evade identification radiologically due to prolonged hydration. The ultimate choice of intervention must be individualised, weighing the risks of retention against the risk of iatrogenic damage.

Evaluation of SARS-CoV-2 in Tears of Patients with Moderate to Severe COVID-19.

PURPOSE: To investigate the presence of SARS-CoV-2 RNA in tears of patients with moderate to severe coronavirus disease 2019 (COVID-19). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with laboratory-proven moderate to severe COVID-19. METHODS: Tears were collected within 48 hours of laboratory confirmation using 3 methods: conjunctival swab plus Schirmer's test strips (group 1), conjunctival swab (group 2), and Schirmer's test strips (group 3). Samples from both the eyes of each patient were transported in a single viral transport media for real-time RT-PCR. Detailed demographic profiles, systemic symptoms, comorbidities, and ocular manifestations were noted. MAIN OUTCOME MEASURES: Viral load of a sample was determined using cycle threshold (Ct) value of E gene. A specimen was considered to show positive results if the amplification curve for the E gene crossed the threshold line within 35 cycles and if it showed positive results on an RNA-dependent RNA polymerase or open reading frame 1b gene assay. RESULTS: Of the 78 patients enrolled in the study, samples from 3 patients were found to be inadequate for analysis. Thirty-six patients (48%) had moderate disease, whereas 39 patients (52%) had severe disease, with no ocular involvement in any patient. In the 75 patients, RT-PCR analysis of tears showed positive results in 18 patients (24%), and 29 of 225 samples (12.9%) showed positive results. Positive results were found in 11 (14.7%), 11 (14.7%), and 7 (9.3%) patients in groups 1, 2, and 3, respectively (P = 0.3105). Mean Ct values in groups 1, 2, and 3 were 28.36 ± 6.15, 29.00 ± 5.58, and 27.86 ± 6.46 (P = 0.92), respectively. Five patients showed positive RT-PCR results by all 3 methods (mean Ct value, 25.24 ± 6.33), and 12 patients showed positive results by any of the 3 methods (mean Ct value, 32.16 ± 1.94), the difference in Ct values being statistically significant (P = 0.029). The median value of symptomatology in patients with positive RT-PCR results from tears was 5 days (range, 4-9 days). CONCLUSIONS: SARS-CoV-2 RNA was detected in tears of 24% of patients with laboratory-proven moderate to severe COVID-19. Conjunctival swab remains the gold standard of tear collection for RT-PCR assay. A significantly higher possibility of viral transmission exists through tears in patients with moderate to severe COVID-19.

In-silico Prediction of the Beta-carboline Alkaloids Harmine and Harmaline as Potent Drug Candidates for the Treatment of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease manifested by core symptoms of loss of motor control and postural instability. Loss of dopaminergic neurons is the cause of PD, thus enhancing dopamine level by pharmacological treatment is one of the key treatment strategies for PD. However, the limitations of current treatment strategies open the possibility of novel drug candidates for the treatment of PD. OBJECTIVE: To investigate the anti-PD potential of Harmine and Harmaline. We aim to evaluate the therapeutic potential of Harmine and Harmaline by in-silico approaches; molecular docking, pharmacokinetic and Prediction of Activity Spectra for Substances (PASS) analysis were used for evaluating the therapeutic potential of Harmine and Harmaline and standard drug levodopa (L-DOPA). METHODS: Auto dock vina was used for molecular docking of all three compounds against D2- and D3- dopamine receptors. The pharmacokinetics (PKs) and toxicity profile were predicted by pkCSM, and the pharmacological activity was predicted by PASS analysis. RESULTS: Molecular docking showed a higher binding affinity of Harmine and Harmaline as compared to L-DOPA, and these results were supported by in-silico pharmacokinetic and toxicity profiling. Moreover, PASS analysis showed anti-PD activity of Harmine and Harmaline. CONCLUSION: Harmine and Harmaline exhibit higher binding affinity towards D2- and D3- dopamine receptors compared to L-DOPA, and PKs and toxicity profile support their potential as drug candidates for PD therapy.

PI-88 and Related Heparan Sulfate Mimetics.

The heparan sulfate mimetic PI-88 (muparfostat) is a complex mixture of sulfated oligosaccharides that was identified in the late 1990s as a potent inhibitor of heparanase. In preclinical animal models it was shown to block angiogenesis, metastasis and tumor growth, and subsequently became the first heparanase inhibitor to enter clinical trials for cancer. It progressed to Phase III trials but ultimately was not approved for use. Herein we summarize the preparation, physicochemical and biological properties of PI-88, and discuss preclinical/clinical and structure-activity relationship studies. In addition, we discuss the PI-88-inspired development of related HS mimetic heparanase inhibitors with improved properties, ultimately leading to the discovery of PG545 (pixatimod) which is currently in clinical trials.

Subthreshold diode micropulse laser versus observation in acute central serous chorioretinopathy.

BACKGROUND: The purpose of this study was to evaluate subthreshold diode micropulse (SDM) laser as a treatment modality in acute central serous chorioretinopathy (CSC) and compare it with the current standard of care (observation). METHODS: A randomised controlled trial was conducted on 68 eyes (34 eyes in SDM laser group and 34 eyes in observation group) with acute CSC, with a single angiographic leak and duration of complaints less than two months. Detailed history, examination and investigations were performed at the baseline and at regular intervals until six months. RESULTS: Eyes in the laser group had significantly higher best-corrected visual acuity at two weeks (p = 0.002), four weeks (p < 0.001), eight weeks (p < 0.001), 16 weeks (p = 0.042) and six months (p = 0.008), and higher contrast sensitivity at eight weeks (p = 0.008), 16 weeks (p < 0.001) and six months (p < 0.001). A recurrent/persistent neurosensory detachment was observed at the end of six months in 11.76 per cent of SDM laser treated eyes versus 29.41 per cent of eyes in the observation group (p = 0.036). CONCLUSION: SDM laser produces faster and superior visual rehabilitation without any adverse effects. It also reduces the chances of CSC going into chronicity and recurrence compared to the current standard of care (observation).

The Development of Assays for Heparanase Enzymatic Activity: Towards a Gold Standard.

The enzyme heparanase, an endo-ß-glucuronidase, degrades heparan sulfate (HS) chains on the cell surface and in the extracellular matrix. Heparanase regulates numerous biological processes that drive tumour growth, metastasis and angiogenesis. In addition to its key role in cancer progression, it has also been implicated in an ever-growing number of other diseases, particularly those associated with inflammation. The importance of heparanase in biology has led to numerous efforts over the years to develop assays to monitor its activity and to screen for new inhibitors as potential drug candidates. Despite these efforts and the commercialization of a few kits, most heparanase assays are still complex, labour intensive, costly or have limited application. Herein we review the various methods for assaying heparanase enzymatic activity, focusing on recent developments towards new assays that hold the promise of accelerating research into this important enzyme.

Abiraterone acetate in the treatment of prostate cancer.

Among all cancer-related death, prostate cancer accounts for the second prominent reason for cancer-associated death in men. Despite the castration mediated reduction in testosterone synthesis, adrenal glands, as well as tissues of prostate cancer, continue to produce androgens, which ultimately lead to the growth of prostate cancer. This phase is referred as metastatic castration-resistant prostate cancer, which throws an obstacle to treatment. Androgen antagonists, in addition to deprivation of hormone, is being used for reducing the level of prostate-specific antigen but has not successfully come in front as a choice for prolonging the life of patients suffering from prostate cancer. In this prevailing scenario, abiraterone acetate (AA) has proved to be a boon for patients suffering from prostate cancer. AA selectively inhibits the actions of enzymes C17, 20-lyase and 17α-hydroxylase on cytochrome P450 (CYP) 17 when administered orally. The signaling of androgen receptor, being important for primary to metastatic phases of prostate cancer, CYP17 is essential for the synthesis of androgen. Herein, the in-detail pharmacological profile of AA, including androgen signaling, mechanism of action of AA, mechanism of AA resistance, pharmacokinetics, latest clinical findings, predictive markers, optimal treatment sequence, toxicity, and food interaction profiles have been reviewed.